Neurobiology of Lipids (ISSN1683-5506) News

Alzheimer's & cholesterol: Problems with low cholesterol pop up

2008-04-22T11:14:00.000+03:00

By Joe Graedon and Teresa Graedon, Ph.D.

What may be good for the heart could be bad for the brain. Lowering cholesterol, especially bad LDL cholesterol, appears to reduce the risk of heart attacks. But new studies suggest that very low cholesterol might pose unexpected problems for the nervous system.

Researchers have analyzed data from a long-term study of Japanese-American men in Honolulu. Blood samples of healthy men were measured in the early 1990s. During the next decade, researchers noted who was diagnosed with Parkinson's disease. Those with low LDL cholesterol initially were significantly more likely to develop this neurological disorder (Movement Disorders online, March 31, 2008).

This is not the first time that low LDL cholesterol has been linked with a higher risk of Parkinson's disease. Other neurological problems also may be associated with low cholesterol. One study uncovered a link between low cholesterol and Alzheimer's disease (Neurology, Aug. 11, 1999).

Scientists in New Zealand have been monitoring adverse effects of cholesterol-lowering medications. They have noted that statins may be associated with depression, memory loss, confusion and aggressive behavior (Drug Safety, March 2007). The authors point out that "Cholesterol is crucial to brain functioning."

A new study (Neurology, March 25, 2008) links low LDL cholesterol to worsening of ALS (Lou Gehrig's disease). In fact, the researchers conclude: "The beneficial effect of hyperlipidemia (high cholesterol) on survival of more than 12 months is, to our knowledge, one of the most important documented."

Probably the most controversial issue hinges on whether lowering cholesterol with statin-type medications is linked to ALS-like syndrome. The French researcher who conducted the study on LDL and ALS, Vincent Meininger, M.D., Ph.D., was asked in a Neurology journal podcast whether there could really be a statin-related ALS connection. He responded, "I think yes."

It is very difficult for scientists to determine whether statin-type medicines trigger or worsen ALS. Many people have reported their experiences to www.peoplespharmacy.com (analyzed in Drug Safety, February 2008).

Here is one example:

"My husband took Lipitor for several years. After a knee replacement, his leg muscle deteriorated, and no amount of exercise could bring it back. Then he developed swallowing problems. He had trouble breathing, but at the emergency room they found nothing wrong.

"He had a lot of pain and no relief even with pain medicine. His muscles weakened so much that he could not eat food unless it was put in a blender. He went from 165 to 113 pounds, losing so much muscle that he fell many times and could only walk with a walker.

"He was an active man before all this happened and exercised every day. He had so many tests to find his problem, but it was not diagnosed as ALS until the morning of the day he died in July 2007. This is a horrible disease and a horrible way to die."

No one knows whether there truly is a relationship between statin-type cholesterol-lowering medicine and ALS-like syndrome. The Food and Drug Administration is investigating this issue. Anyone who would like to report serious problems with such medications can do so at the FDA's Web site (www.fda.gov/medwatch)....

Source: Joe Graedon and Teresa Graedon. Problems with low cholesterol pop up. King Features Syndicate (20 April 2008) [FullText and Q&A section]

Results from Largest Statin Study of Patients with Alzheimer's Disease Show Lipitor(R) Has No Significant Impact on Disease

2008-04-16T11:11:00.002+03:00

NEW YORK, Apr 16, 2008 (BUSINESS WIRE) -- In a study in patients with mild-to-moderate Alzheimer's disease (AD), the addition of Lipitor (atorvastatin calcium tablets) 80 mg to Aricept(R: 67.12, +3.05, +4.76%) (donepezil HCl) 10 mg showed no significant differences in cognition or global function (key measures of Alzheimer's progression) compared to placebo plus Aricept 10 mg. Furthermore, no statistically significant differences were seen on various cognitive, behavioral and functional secondary endpoints. However, the Lipitor arm was not associated with greater cognitive decline than the placebo arm in this trial. The results were presented today at the annual American Academy of Neurology meeting in Chicago.

The 18-month study, called Lipitor's Effect on Alzheimer's Dementia (LEADe), included 640 patients and is the largest statin study in Alzheimer's disease.

While rates of decline in cognition and global function were similar for both the Lipitor and placebo groups, there were some interesting findings from the trial:

In a sub set of 64 patients for whom MRI scans were available, patients in the Lipitor arm had significantly less decline in hippocampal volume in the brain compared to the placebo arm. While the clinical significance of this result is not yet fully understood, less decline in hippocampal volume may be beneficial since declines have been associated with the progression of Alzheimer's disease. This finding requires further investigation and analysis.

In a sub-analysis completed after the trial, men in the Lipitor arm had a significantly slower rate of decline in cognition compared to men in the placebo arm. There was no difference in the rate of decline in cognition in women in the Lipitor arm compared to women in the placebo arm. However, no definitive conclusions can be drawn from this post-hoc analysis.

"The results of our investigation of Lipitor on the symptoms of Alzheimer's disease have been long awaited," said Professor Howard Feldman, chair of the LEADe Steering Committee and professor and head of the division of neurology, University of British Columbia Hospital in Canada. "While the LEADe study did not demonstrate significant benefits on the symptoms of mild to moderate Alzheimer's disease, there are some noteworthy findings that require further analysis and should inform further research to determine the potential for statin use in this population."

Lipitor 80 mg was shown to be well tolerated and the incidence of liver and muscle adverse events in patients was low.

Aricept was selected as the background therapy since it is proven effective for treating the symptoms of Alzheimer's and is the most widely used cholinesterase inhibitor. The effect of Aricept on Alzheimer's was not investigated in this study.

"Over the past 15 years, Pfizer has been committed to researching the potential benefit of Lipitor in patients at various levels of cardiovascular risk as well as in non cardiovascular diseases such as Alzheimer's disease," said Dr. Rochelle Chaiken, vice president of the cardiovascular/metabolic team in Pfizer global medical. "While we are not planning additional studies with Lipitor in patients with Alzheimer's disease at this time, LEADe provides the medical community with important data. In addition, Pfizer is committed to advancing research and treatment in Alzheimer's disease."

About Alzheimer's Disease

Alzheimer's disease is a progressive degenerative brain disorder that gradually destroys a person's memory and ability to learn, reason, make judgments, communicate, and carry out daily activities. As the disease progresses, patient may experience changes in personality and behavior, such as anxiety, suspiciousness or agitation, as well as delusions or hallucinations.

About Lipitor

Lipitor is the most prescribed cholesterol-lowering therapy in the world, with nearly 144 million patient-years of experience. Lipitor is supported by an extensive clinical trial program involving more than 400 ongoing and completed trials with more than 80,000 patients.

Important U.S. Prescribing Information for Lipitor

Lipitor is a prescription medication. It is used in patients with multiple risk factors for heart disease such as family history, high blood pressure, age, low HDL ("good" cholesterol) or smoking to reduce the risk of a heart attack, stroke, certain types of heart surgery and chest pain.

Lipitor is also used in patients with type 2 diabetes and at least one other risk factor for heart disease such as high blood pressure, smoking or complications of diabetes, including eye disease and protein in urine, to reduce the risk of heart attack and stroke.

Lipitor is used in patients with existing coronary heart disease to reduce the risk of heart attack, stroke, certain kinds of heartsurgery, hospitalization for heart failure, and chest pain.

When diet and exercise alone are not enough, Lipitor is used along with a low-fat diet and exercise to lower cholesterol.

Lipitor is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, pregnant or may become pregnant.

Patients taking Lipitor should tell their doctors if they feel any new muscle pain or weakness. This could be a sign of rare but serious muscle side effects. Patients should tell their doctors about all medications they take. This may help avoid serious drug interactions. Doctors should do blood tests to check liver function before and during treatment and may adjust the dose. The most common side effects are gas, constipation, stomach pain and heartburn. They tend to be mild and often go away.

For additional product information, visit Lipitor.com.

About Aricept

Once-a-day prescription ARICEPT(R: 67.12, +3.05, +4.76%) (donepezil HCl tablets) is indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate and severe Alzheimer's disease (AD). ARICEPT helps with memory, thinking and everyday tasks.

ARICEPT is the number-one prescribed AD medication worldwide, with more than 3 billion patient days of ARICEPT therapy sold. Nearly 2.3 million people in the United States alone have begun ARICEPT therapy.

Important U.S. Prescribing Information for Aricept

ARICEPT is the first once-a-day Alzheimer's prescription medication available in the U.S. and can be taken with or without food. Available in 5 mg or 10 mg dosage strengths, ARICEPT 5 mg and 10 mg are approved for the treatment of mild to moderate AD. ARICEPT 10 mg (after four to six weeks at 5 mg) is approved for the treatment of severe AD. ARICEPT(R: 67.12, +3.05, +4.76%) ODT(TM: 101.55, +2.98, +3.02%) (donepezil HCl) Orally Disintegrating Tablets are available in the U.S. in 5 mg and 10 mg tablets, providing the same dosage strength of drug as ARICEPT tablets.

ARICEPT is well tolerated but may not be for everyone. People at risk for stomach ulcers or who take certain other medicines should tell their doctors because serious stomach problems, such as bleeding, may get worse. Some people who take ARICEPT may experience fainting. Some people may have nausea, vomiting, diarrhea, bruising, or not sleep well. Some people may have muscle cramps or loss of appetite or may feel tired. In studies, these were usually mild and temporary.

For additional product information, visit aricept.com

SOURCE: Pfizer Inc: Pfizer Vanessa Aristide, 212-733-3784 or Rebecca Hamm, 212-733-8811 Copyright Business Wire 2008

Also see: Pfizer's Lipitor Failed to Slow Alzheimer's Disease in Study

Connection between Molecules Involved in Early- and Late-Onset Alzheimer’s Discovered

2007-10-07T18:14:00.000+02:00

Researchers at Washington University School of Medicine in St. Louis found an aspect of cholesterol transport and metabolism in the brain that links molecules involved in early- and late-onset Alzheimer’s disease (Neuron, October 1, 2007, see NoL noteworthy colelction).

The scientists believe that their study strengthens the case for another cause of Alzheimer’s besides build up of amyloid-beta (A-beta) plaques. “Cholesterol metabolism in the brain is an understudied area, and our findings could inspire Alzheimer’s researchers to look further into the role of the cholesterol pathway,” says senior author Guojun Bu, Ph.D., professor of pediatrics and cell biology and physiology.

Early-onset Alzheimer’s can be traced to mutations in one of three genes including the gene coding for A-beta’s precursor, APP. The genetic origins of late-onset Alzheimer’s are unknown, but studies have shown that a particular mutation in the gene for a cholesterol carrier, called apolipoprotein E, increases risk.

The Washington University team report that when APP is cleaved by gamma-secretase in the brain, it releases A-beta plus a small protein fragment, APP intracellular domain (AICD). AICD regulates apolipoprotein E, which moves cholesterol in the brain from support cells to neurons, through the lipoprotein receptor LRP1.

“Right now,” Dr. Bu adds, “research on Alzheimer’s treatment focuses largely on reducing A-beta production or increasing its clearance from the brain. Our study suggests that there could be an alternate way to treat the disease, perhaps by modulating the function of apolipoprotein E and cholesterol in the brain.”

Source: Connection between Molecules Involved in Early- and Late-Onset Alzheimer’s Discovered. GEN News Highlights (5 October 2007) [FullText]

Brain, Eye and Heart Health: Three Reasons to Eat More Omega-3s

2007-10-05T18:14:00.000+02:00

DENVER, 3 October 2007 (PRNewswire) - Most pregnant women consuming a typical western diet obtain too little DHA (docosahexaenoic acid), a major marine omega-3 fatty acid, which is critical for fetal and infant brain development. This was the conclusion of a landmark report from an international panel of nutrition experts summarized in the September 2007 Fats of Life and PUFA Newsletter electronic publications. The report called for pregnant and lactating women to consume at least 200 mg of DHA/day. It also noted that higher maternal intakes of DHA are linked to better visual acuity, cognitive function, sleep patterns and other benefits.

Another study discussed in the e-newsletters found that mothers at high-risk of preterm delivery may lower their chance of giving birth early by increasing their intake of marine omega-3s. Moreover, the breast milk content of DHA in mothers from around the world was the lowest in countries where little fish is consumed, such as the U.S. and Canada.

"Many, if not most, women are not consuming enough DHA," said Joyce Nettleton, DSc, editor of Fats of Life and the PUFA Newsletter. "This is especially true in western countries."

Seeing is believing when it comes to marine omega-3s and eye health. A US study revealed that animals at risk of retinal damage were better protected from vision loss if they consumed diets high in marine omega-3s.

Other recent research reported that a key region of the brain affected by mood disorders has significantly less DHA in people suffering from major depression compared with those who are not depressed. There is also new evidence that cognitive function in later life may be partly protected when marine omega-3s are more abundant.

Finally, the e-newsletters report that DHA, along with the omega-3 EPA (eicosapentaenoic acid), enhances the effectiveness of statin drugs in patients with high cholesterol and triglycerides by lowering triglycerides significantly, according to an Australian study. Statins alone have little effect on triglyceride levels.

The bottom line: boosting one's marine omega-3 intake may improve brain development and function and protect the eyes and heart from disease damage. Learn more in the latest issues of the quarterly Fats of Life e-newsletter and PUFA Newsletter. These publications, sponsored by DSM Nutritional Products, are online at www.fatsoflife.com and by complimentary subscription.

Source: Fats of Life, Source: PR Newswire (3 October 2007) [FullText]

Neurobiology of Lipids Fourth Anniversary: Scope Expanded, Subject Postscript Archive Mission Taken

2006-04-07T02:15:00.000+03:00

Dear Colleagues and Friends,

I am writing to inform you that Neurobiology of Lipids is expanding its' scope.

In addition to the publication of original research articles, review articles, commentaries, correspondence arising matters and all other type of manuscripts, NoL will be archiving original research articles (on the subject of the neurobiology of lipids) published in other journals.

A year ago Neurobiology of Lipids welcomed National Institutes of Health (NIH) new policy on Public Access effective May 3, 2005 (see NoL Newsstand 6 February 2006). A year latter the first Report on the NIH Public Access Policy showed the policy compliance rate is 3.8 %. It means that just "three point eight percent of the literature that was eligible for archiving under the NIH Public Acces policy actually got archived in NIH PubMedCentral (PMC). This is despite NIH did its level best to communicate the policy to researchers, and they’re decently competent at outreach." In contrast, for-profit publishers didn’t spread much info on NIH policy among researchers. While the policy had no teeth and researchers don’t understand and don’t care about the economics or socioinformatics of publishing, we hope the benefits of archiving your original research article in NoL are compelling.

First, you will retain the publication impact of the original journal (Science, Nature, PNAS, Journal of Lipid Research, FASEB Journal, Neurology, or any other journal that you selected as the first place of publication and succeded publishing at).

We realise the lack of comparable impact by the Neurobiology of Lipids is the major reason you feel hesitant to submit your best data to NoL. We feel happy pre-publication inquiries and recent submissions indicate there is a change for good. We further hope that NoL archiving of your articles published elsewhere will help to bridge the gap between your willingness to have your major data published in major journals, and your possible interest to contribute to NoL.

Second, you will have article archived at the Neurobiology of Lipids, the major subject publication, where it will be accessible to everyone for free.

What is the readership of the Neurobiology of Lipids? We hope that NoL home page visitors world map (available in smaller or bigger clusters) and article access statistics (available at the journal home page) will point you to the answer. The following data may be of additional interest (aslo see the journal page "Why publish in NoL?").

By now we have established several avenues of dissemination to ensure great readership. Published papers are promoted by Neurobiology of Lipids content alert email service (presently 970 individual subscribers working on the subject of the journal scope). Neurobiology of Lipids articles are indexed at the Chemical Abstracts (a service by American Chemical Society), the Directory of Open Access Journals (DOAJ), and in all major universal web search engines including Yahoo, Google and academic Google Scholar and Elsevier Scirus. At Google, NoL home page rank is 6 of 10 (compare with the Google rank value of 7/10, 8/10, and 9/10 for Journal of Lipid Research, Journal of Biological Chemistry and PNAS, for example). Neurobiology of Lipids is also indexed in great number of academic libraries worldwide, Harvard Open URL generator, Serials Solutions, Bowker Ulrich's Periodicals Directory, NIH NLM catalog, EBSCO A-to-Z service, BIOSIS Biology Browser, and subject resources, such as the paper of the week collection by Alzheimer Research Forum (that has 3000+ current subscribers). NoL articles are well cited as judged by ISI Web of Knowledge Science Citation index. This will provide additional citation opportunity when your original research report is archived in NoL. As we informed you previously, last year NIH PubMedCentral (PMC) welcomed NoL to work on meeting technical requirements of the journal archiving in PMC. We will continue working on PubMedCentral archiving immediately after we know (in June 2006) about the decision on the Grant proposal by NoL managing editor, having NoL archiving in PMC as one of the specific aims of this Open Access project.

Third, easy submission for archiving in NoL

NoL will consider for archiving the original research articles, peer-reviewed and published in other journals before submission for NoL archive. When your article is in press, and the proofs are corrected, it will be natural to consider submitting the corrected final article text file and image files to NoL for archiving (along with the "Manuscript Registration" form submission to be modified to allow archiving submission by April 12, Neurobiology of Lipids 4th anniversary). We will process your article to yield NoL archived article in .HTML, Adobe .PDF, and NIH DTD .XML format. The article will be labelled with the " Neurobiology of Lipids Archive" article prefix and will indicate peer-review was performed by the original place of publication along with full citation details of original publication.

To ensure the original publisher is duly identified, you will have to submit to NoL complete citation information, such as journal title, ISSN number, volume and issue numbers, date, paging, DOI, PubMed ID, and hyperlink (URL) to the article on the Publisher/other web site(s).

Forth, the independence pleasure of liberating your scholar output from commercial publisher cabal, making your research freely available to peers and the public:

As a part of article submission for NoL archive, you will have to verify your copyright. Because your article has been published previously, check your copyright transfer form to be sure you have the right to post it. Check current policies of your publisher, because new regulations may override the terms you accepted in the past and presently allow archiving. If it is a work of multiple authorship, ascertain that the other authors also approve article archiving at NoL.

Understanding Neurobiology of Lipids major archiving term is also important. At present many for-profit and learned societies' scientific publishers allow self archiving and Institutional archiving of scholar works. See specific language of the self-archiving policy by Elsevier and Science magazine by AAAS. The latter source further says, that in order "to qualify as a personal web site the site must be devoted to the author's research and owned by the author (or if the author's employer is a non-profit institution, owned by that institution)." To meet such requirement by publishers you will have to agree (upon submission of your article for NoL archiving) with "personal website" definition of your NoL postscript archive web folder, the publication unit of Neurobiology of Lipids. Archived article folder, however, will retain the standard structure of NoL publications, such as <www.neurobiologyoflipids.org/content/4/3> , for example.

As a part of your submission, you will also have to grant to NoL, the right to disseminate your article postscript, provided that the integrity of the article is guaranteed, that the original publisher is duly identified, and that proper attribution of authorship and correct complete citation details are endorsed on the postscript publication.

Because of universal free open access to your article, we do not believe archiving in NoL will create a redundant publication

Conclusion

As a result of your article archiving in NoL, it will become belonging (in addition to your pride of original publication elsewhere) to a so called Open Access domain, freely available for both peers and the public. I therefore feel confident NoL archiving of your article won't create a redundant publication. Will it yield any harm other then the increase of your readership, article usage and future citation impact? The answer rests with you.

Sincerely,

Alexei Koudinov, MD, PhD
Editor
Neurobiology of Lipids (ISSN 1683-5506)
www.neurobiologyoflipids.org

Neurobiology of Lipids welcomes the new National Institutes of Health Public Access policy

2005-02-06T17:21:00.000+02:00

Neurobiology of Lipids (NoL) welcomes the announcement by the National Institutes of Health (NIH) new "Policy on Enhancing Public Access to Archived Publications Resulting from NIH-Funded Research" effective May 2, 2005. The NIH requests the Agency grant recipients to deposit resulting publications in the National Library of Medicine's PubMed Central (PMC, a free governmental archive of the life sciences literature) within 12 months since originally published in a peer-reviewed journal.

The article deposition in NIH archive will no doubt benefit the scholars themselves. This is because deposition in PMC archive will ensure the publication is preserved for future generations and gets maximum and barrier-free exposure to both peers and the public. For the Policy wording on these and other issues (such as reliability of article access at PMC site and their integration with other NIH Databases) please see original NIH document:

Policy on Enhancing Public Access to Archived Publications Resulting from NIH-Funded Research.
Notice Number: NOT-OD-05-022 (Release Date: February 3, 2005; Effective Date: May 2, 2005).
Issued by National Institutes of Health (NIH)
Available at:

While the new Policy calls for the voluntary submission of final author manuscripts and does not affect the ability to copyright, all NIH grantees now have a new issue to consider when selecting the journal to publish at. To fulfill the NIH request, authors publishing in the majority of the traditional journals (i.e. those where authors transfer copyright to the publisher) will have to go through a process of resubmitting their papers to the PubMed Central archive. Moreover, the authors will often need to select for PMC archive the manuscript version with the changes introduced during the publication procedure, because many publishers (ex. Elsevier) allow archiving of the author's version of the manuscript only.

Neurobiology of Lipids has met the National Library of Medicine quality requirement for PubMed Central archiving and is presently successfully working on bringing its' prior publications' collection into the Extensible Markup Language (XML) files' format (suitable for deposition in PMC) using just released latest version 2.0 of the National Library of Medicine XML Document Type Definition (DTD) for journal publishing.

While taking the advantage of an irreversible Internet and desktop publishing technology development and their end user availability at almost no cost, Neurobiology of Lipids is also originating the research project aiming to develop the software tool that will make direct publishing (to an appropriate XML file compliant with NIH DTD) as simple, as web form submission (that any of you use while performing on-line bank transaction, interlibrary loan request, an Institution internal services operation or thousand other purposes). Such tool will be essential for independent journals (encouraged by Neurobiology of Lipids and similarly built on a concept of a non-profit model for cost-effective independent scholar journals), their authors, Academic Institutions setting their own archives, and individual scientists, willing to deposit their articles in a modern XML file format. NoL is open for partnership by any interested party and has open opportunities for Graduate students to participate in this and other projects.

Therefore, when Neurobiology of Lipids archiving in PMC is implemented, any article published in the journal will meet the NIH new Policy, immediately and without any need for additional archiving works by authors.

Starting this week XML files for NoL articles will be also available at NoL (as an additional link at articles' web pages) and offered for syndication (as it was earlier implemented for NoL Global Newsstand, indexing NoL articles' abstracts and NoL noteworthy articles published in other journals). Our authors will thus save the time and effort of going through the deposition process themselves. The other benefits of publishing in NoL include the rapid, fair and quality peer review, fast publication and high visibility of Neurobiology of Lipids among those working in the filed (as verified by NoL readership of about 1/3-1/4 of the readership of the major Journal of Lipid Research published since 1959) and wide geographical distribution of NoL readers (Neurobiol Lipids World Reader's Map can be viewed by clicking on a map logo at the bottom of the journal home page).

Another opportunity offered by NIH PMC archiving is to link an article to any other publication via related article feature of the DTD. This feature creates an important technical background for NoL call for commentaries and letters to the editor on related/noteworthy articles appeared in other journals. The NIH DTD feature will make sure such communication arising matters when published in NoL are linked in NIH databases to original publications in other journals.

Surely, Neurobiology of Lipids welcomes researchers in the field of neuroscience of fats to consider publishing in the Neurobiology of Lipids all types of articles, and to consider for publication other journals depositing full text articles (not just abstracts!) in PubMed Central.

Neurobiology of Lipids also urges funding bodies worldwide to follow the pioneering NIH policy, and welcomes industry members to consider establishing funds to support authors publishing in NoL.

Further info/contact:

Alexei Koudinov, MD, PhD
Editor
Neurobiology of Lipids

P.O.Box 1665
Rehovot 76100
Israel

Cholesterol cures Alzheimer's

2004-12-08T11:49:00.001+02:00

Citation: Abad-Rodriguez J, Ledesma MD, Craessaerts K, Perga S, Medina M, Delacourte A, Dingwall C, De Strooper B, Dotti CG. Neuronal membrane cholesterol loss enhances amyloid peptide generation. J Cell Biology Vol.167(5), 953-960 (6 December 2004) [Further details]

Abstract: Recent experimental and clinical retrospective studies support the view that reduction of brain cholesterol protects against Alzheimer's disease (AD). However, genetic and pharmacological evidence indicates that low brain cholesterol leads to neurodegeneration. This apparent contradiction prompted us to analyze the role of neuronal cholesterol in amyloid peptide generation in experimental systems that closely resemble physiological and pathological situations. We show that, in the hippocampus of control human and transgenic mice, only a small pool of endogenous APP and its beta-secretase, BACE 1, are found in the same membrane environment. Much higher levels of BACE 1-APP colocalization is found in hippocampal membranes from AD patients or in rodent hippocampal neurons with a moderate reduction of membrane cholesterol. Their increased colocalization is associated with elevated production of amyloid peptide. These results suggest that loss of neuronal membrane cholesterol contributes to excessive amyloidogenesis in AD and pave the way for the identification of the cause of cholesterol loss and for the development of specific therapeutic strategies.

Authors: Jose Abad-Rodriguez, Maria Dolores Ledesma, Katleen Craessaerts, Simona Perga, Miguel Medina, Andre Delacourte, Colin Dingwall, Bart De Strooper, and Carlos G. Dotti

Authors Institution: Cavalieri Ottolenghi Scientific Institute, Universita degli Studi di Torino, 10043 Orbassano (TO), Italy; Center for Human Genetics, Catholic University of Leuven and Flanders Interuniversitary Institute for Biotechnology, 3000 Leuven, Belgium; Unité INSERM 422, Lille, France; Neurology and GI CEDD, GlaxoSmithKline Pharmaceuticals, Harlow, Essex CM195AW, England, UK

Key words: Alzheimer's disease; cholesterol; lipids; synaptic function; neuron; neural plasticity; neurodegeneration; memory loss; amyloid; secretases;

Key note by Jose Abad-Rodriguez and Maria-Dolores Ledesma: "We here provide evidence that cholesterol-rich membrane domains (rafts) act as "basins" to segregate the APP-b-secretase BACE from its substrate APP. A mild but significant reduction of membrane cholesterol observed in Alzheimer's disease patient brains or induced in cultured neurons, leads to raft disorganization. Such an alteration results in increased amyloid production. These data suggest that approaches aimed to prevent neuronal cholesterol loss, contrarily to what has been proposed, should be taken into account when considering AD treatments."

Further reading: see related articles at Neurobiology of Lipids.

Serum lipids and hippocampal volume: The link to Alzheimer's disease?

2004-11-16T11:55:00.000+02:00

Citation: Wolf H, Hensel A, Arendt T, Kivipelto M, Winblad B, Gertz HJ. Serum lipids and hippocampal volume: The link to Alzheimer's disease? Ann Neurol. 56(5), 745-749 (25 Oct 2004) . doi: 10.1002/ana.20289.

Abstract: The association between hippocampal volume (as a presumed index of Alzheimer's disease pathology) with serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was studied in 86 elderly subjects with a range of cognitive functions. High-density lipoprotein cholesterol, but not low-density lipoprotein cholesterol or total cholesterol, was associated with hippocampal volume and dementia. This is compatible with protective effects of high-density lipoprotein cholesterol on hippocampal atrophy and Alzheimer's disease.

Authors: Henrike Wolf, MD, PhD; Anke Hensel, DP; Thomas Arendt, MD, PhD; Miia Kivipelto, MD, PhD; Bengt Winblad, MD, PhD; Hermann-Josef Gertz, MD, PhD
Authors Institution: Department of Neurotec, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden, e.mail: henrike.wolf[at]neurotec.ki.se ; Department of Psychiatry, University of Leipzig, Leipzig, Germany; Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany

First author key note: "Disturbances in brain cholesterol metabolism have been associated with all principal pathological features of Alzheimer's disease (AD). Although serum and brain cholesterol are classically believed to be independent, some studies suggested a link between serum cholesterol and AD-like pathology or risk of dementia. In light of these findings, we studied the association between hippocampal volume – as a presumed index of AD pathologyv- and serum cholesterol in 86 elderly subjects with a range of cognitive functions. Serum HDL-cholesterol, but not LDL- or total cholesterol, was associated with hippocampal volume and dementia. This is compatible with protective effects of HDL-cholesterol on hippocampal atrophy and Alzheimer's disease. The finding could reflect the role of cholesterol and lipoproteins in facilitating synaptic plasticity in the aging human brain."

Further reading: see related articles at Neurobiology of Lipids.

Scientists, consider where you publish

2004-11-15T13:33:00.000+02:00

Citation: Seringhaus M. Scientists, consider where you publish. Neurobiol Lipids Vol. 3, 10 (2 Nov 2004). Available at: http://neurobiologyoflipids.org/content/3/10/

Abstract: For scientists, publishing a paper in a respected peer-reviewed journal marks the culmination of successful research. But some of the most prestigious and sought-after journals are so costly to access that a growing number of academic libraries can't afford to subscribe. Before submitting your next manuscript, consider a journal's access policy alongside its prestige - and weigh the implications of publishing in such costly periodicals. Two distinct problems continue to plague scientific publishing. First, institutional journal subscription costs are skyrocketing so fast that they outstrip the ability of many libraries to pay, threatening to sever scientists from the literature. Second, the taxpaying public funds a terrific amount of research in this country, and with few exceptions, can't access any of it. These problems share a common root - paid access to the scientific literature.

Author: Michael Seringhaus
Authors Institution: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven CT 06520 USA. e.mail: michael.seringhaus[at]yale.edu

Key words: Free open access; STM journals archives publishing; institutional repositories; Public Library of Science PLoS; BioMed Central; PubMed Central PMC; SPARC; access price permission barrier; serials pricing crisis; US Congress; science policy; Elsevier Cell Press Immunity Neuron

Association of Research Libraries (ARL) official comments on National Institutes of Health (NIH) public access proposal

2004-11-15T13:29:00.000+02:00

Citation: Adler PS. Association of Research Libraries (ARL) official comments on National Institutes of Health (NIH) public access proposal. Neurobiol Lipids Vol. 3, 9 (2 Nov 2004). Available at: http://neurobiologyoflipids.org/content/3/9/

Abstract: I am writing on behalf of the Association of Research Libraries (ARL) to express our strong support for the National Institutes of Health (NIH) proposal to provide freely available online access to NIH-funded manuscripts via PubMed Central, http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-04-064.html. There are many aspects of the NIH plan that ARL endorses and ARL applauds NIH's leadership in promoting this balanced initiative. There are six issues concerning the NIH plan that are the focus of ARL’s comments, including how the proposal: reflects the way scientists conduct research and discovery; allows some libraries to provide additional resources to their users; creates an archival resource for biomedical literature funded by NIH; provides significant protections to commercial and not-for-profit publishers; follows congressional and administration policy; and expands and improves public access to biomedical information.

Author: Prudence S. Adler
Authors Institution: Associate Executive Director, Association of Research Libraries, 21 Dupont Circle, Suite 800, Washington, D.C. 20036, USA, e.mail: prue[at]arl.org

Key words: Free open access; STM journals archives publishing; institutional repositories; Public Library of Science PLoS; BioMed Central; PubMed Central PMC; SPARC; access price permission barrier; serials pricing crisis; US Congress; science policy; Elsevier

34th Society for Neuroscience Annual Meeting neurobiology of lipids sessions 2004

2004-11-15T13:27:00.000+02:00

Citation: Editorial Material. 34th Society for Neuroscience Annual Meeting neurobiology of lipids sessions 2004. Neurobiol Lipids Vol. 3, 5 (13 Sep 2004). Available at: http://neurobiologyoflipids.org/content/3/5/

Abstract: This article alerts interested readers about neurobiology of lipids sessions of the 34th Society for Neuroscience (SfN) annual meeting, 23-27 October, 2004, San Diego, CA. The abstracts were retrieved from the SfN web based abstract system as a result of the search for the key words cholesterol, phospholipid, lipoprotein, apolipoprotein, fatty acid, lipid, lipid peroxidation in abstract title/key words, abstract text or session title. The reference to each abstract entry includes day/time, program number, presentation type, location, authors list, first author first affiliation, and the abstract title. Each abstract title provides link to abstract text at the scholarone.com web site. The presented list yielded editors' choice short list of noteworthy presentations. All abstracts' authors were invited to publish peer-reviewed proceedings articles in the Neurobiology of Lipids.

Author: Editorial Material
Authors Institution: Neurobiology of Lipids, P.O.Box 1665 Rehovot 76100, Israel; sfnabstracts[at]neurobiologyoflipids.org

Key words: neuroscience of lipids; literature update; cholesterol; fatty acids; fa; srebp; lxr; phospholipids; lipoprotein; lipid peroxidation; psychiatry; neurology; receptor; amyloid hypothesis; Alzheimer's disease; Down syndrome; synapse; synaptic plasticity

The use of fatty acid supplementation for seizure management

2004-11-15T13:24:00.000+02:00

Citation: Mostofsky DI et al. The use of fatty acid supplementation for seizure management. Neurobiol Lipids Vol. 3, 4 (20 Oct 2004). Available at: http://neurobiologyoflipids.org/content/3/4/

Abstract: Impressive research demonstrates the importance of essential fatty acids (FA) for many physiological and behavioral mechanisms, in both humans and animals. In humans, essential fatty acids must be supplied via the diet. The genesis, maintenance, exacerbation, and treatment for many chronic health conditions are often related to deficiencies in omega-6 (linoleic acid) and omega-3 (alpha-linolenic acid), and their derivatives. In animal studies, providing supplementation of these FA changes chemical, immune, and structural properties of the brain, including the fluidity of the neuronal membrane. Of particular interest to epilepsy, pre-treatment of a ratio of the FA omega-3 / omega-6 resulted in altering the threshold for seizures following administration of convulsant agents that reliably induce epileptic activity. This report reviews the human and animal clinical and experimental data and theoretical considerations that support the promise for FA supplementation for use by seizure patients.

Author: David I. Mostofsky and colleagues
Authors Institution: Department of Psychology, Boston University, Boston, MA

Key words: fatty acids; FA; polyunsaturated fatty acids; ketogenic diet; omega-3; omega-6; seizures; membrane fluidity; epilepsy; anti-epileptic drug; cortisol; stress; blood-brain barrier; BBB; elongation; linoleic acid; alpha-linoleic acid; n-3; n-6

Pierre Morell tribute for neurobiology of lipids

2004-11-15T13:21:00.000+02:00

Citation: Toews A, Jurevics H. Pierre Morell tribute for neurobiology of lipids. Neurobiol Lipids Vol. 3, 3 (19 May 2004). Available at: http://neurobiologyoflipids.org/content/3/3/

Abstract: Pierre Morell, Professor of Biochemistry and Biophysics at the University of North Carolina-Chapel Hill, passed away on July 15, 2003 after a brief illness. Pierre was educated at the Bronx High School of Science, Columbia University, and The Albert Einstein College of Medicine, doing post-doctoral research with Norm Radin at the University of Michigan-Ann Arbor. Pierre was a leader in the field of myelin metabolism, in particular the synthesis and turnover of myelin lipids (glycosphingo-lipids, phospholipids, cholesterol). A re-curring theme was use of altered states (e.g., mutant or genetically engineered mice, toxicants, altered nutritional states) to examine myelin metabolism and function. He was a tireless supporter of various scientific societies, including the International Society for Neurochemistry, and he provided wise counsel and advice to several generations of neuroscientists throughout the world. His premature passing has left a void that will be difficult to fill. A memorial fund at UNC has been established.

Author: Arrel Toews and Helga Jurevics
Authors Institution: University of North Carolina (UNC) Neuroscience Center, CB# 7250, Chapel Hill, NC 27599-7250, USA, atoews[at]med.unc.edu

Key words: memoriam; myelin; demyelination; glycosphingolipids; cerebroside; sulfatide; tellurium; Cuprizone; remyelination; cholesterol; phospholipids; lipid synthesis; lipid turnover; myelin metabolism; myelin gene expression; mutant mice; PLPnull; axonal transport

Open letter to President George W. Bush on conduct by scientists, STM journals, and Scientific Institutions

2004-11-15T13:16:00.000+02:00

Citation: Koudinov AR. Open letter to President George W. Bush on conduct by scientists, STM journals, and Scientific Institutions. Neurobiol Lipids Vol. 3, 2 (10 March 2004). Available at: http://neurobiologyoflipids.org/content/3/2/

Abstract: Several recent publications in Science magazine seem supporting the "campaign to stop [George W. Bush Administration] misuse of science before it damages our health, safety, and environment." This open letter to The President argues that the major threat to the public health and public interest in science come from corrupted scientists, STM journals and scientific institutions. The letter quotes the author written evidence for inquiry on Scientific Publication by Science and Technology Committee, UK House of Commons. This evidence analyses the state of affairs in Alzheimer's disease (AD) research, concludes on "editorial and publisher corruption" by the major general science and neuroscience journals, and serves the basis for a referring the major conflict of interest in the field of AD for UK Serious Fraud Office investigation. The letter invites The President to lead the task to correct the situation and to help to restore integrity of science at all stages of scientific process.

Author: Alexei R. Koudinov
Authors Institution: Russian Academy of Medical Sciences, c/o P.O.Box 1665, Rehovot 76100 Israel, alexeikoudinov[at]neurobiologyoflipids.org

Key words: Alzheimer's disease; Niemann Pick type C disease; NPC; Potamkin prize; institutional corruption in medicine; public interest; public health; ethics; behavior; non disclosure; competing financial interest; Administration; scientific integrity; political; appointment; faculty; university; policymaking

Induction of cholesterol efflux in the CNS

2004-11-15T13:11:00.000+02:00

Citation: Rebeck WG. Induction of cholesterol efflux in the CNS. Neurobiol Lipids Vol. 3, 1 (29 Feb 2004). Available at: http://neurobiologyoflipids.org/content/3/1/

Abstract: Intricate cellular mechanisms exist for maintaining proper cholesterol levels. Several recent studies of removal of excess cholesterol in the CNS have focused on the ABC-A1 lipid transporter and its regulation via the LXR nuclear hormone receptor. Cellular cholesterol is hydroxylated to form oxysterols (24-hydroxycholesterol in the brain), which bind LXR and promote gene transcription. LXR activation increases levels of ABC-A1 and apoE, which together act to remove cholesterol and other lipids from cells. Recent studies including Liang et al. suggest manipulation of the LXR system alters brain cholesterol homeostasis and apoE levels, and thus could be beneficial in approaches to Alzheimer disease therapeutics.

Author: G. William Rebeck
Authors Institution: Department of Neuroscience, Georgetown University, 3970 Reservoir Rd, NW, Washington, DC 20057-1464 USA

Key words: apolipoprotein; apoE; ABC-A1; LXR; oxysterols; Alzheimer's disease; cholesterol homeostasis efflux; neurodegeneration; lipoprotein; apolipoprotein; LRP; Down' syndrome; ApoE4; HMGCoA reductase; lipids; LDLr; LRP receptor; injury; Niemann Pick C (NPC)

33rd Society for Neuroscience annual meeting neurobiology of lipids sessions 2003

2004-11-15T13:08:00.000+02:00

Citation: Editorial Material. 33rd Society for Neuroscience annual meeting neurobiology of lipids sessions 2003. Neurobiol Lipids Vol. 2, 3 (1 Oct 2003). Available at: http://neurobiologyoflipids.org/content/2/3/

Abstract: This article alerts interested readers about neurobiology of lipids sessions of the 33rd Society for Neuroscience (SfN) annual meeting, 8-12 November, 2003, New Orleans, LA. The abstracts were retrieved from the SfN web based abstract system as a result of the search for the key words cholesterol, phospholipid, lipoprotein, apolipoprotein, fatty acid, lipid, lipid peroxidation in abstract title/key words, abstract text or session title. The reference to each abstract entry includes day/time, program number, presentation type, location, authors list, first author first affiliation, and the abstract title. Each abstract title provides link to abstract text at the scholarone.com web site. The presented list yielded editors' choice short list of twenty noteworthy presentations. The short listed abstracts were invited to publish proceedings and lay language articles at the Neurobiology of Lipids.

Author: Editorial Material
Authors Institution: Neurobiology of Lipids, P.O.Box 1665 Rehovot 76100, Israel; sfnabstracts[at]neurobiologyoflipids.org

Key words: neuroscience of lipids; literature update; cholesterol; fatty acids; FA; SREBP; LXR; phospholipids; lipoprotein; lipid peroxidation; psychiatry; neurology

Polymorphisms in genes of proteins involved in cholesterol metabolism: evidence for Alzheimer's disease?

2004-11-15T13:04:00.000+02:00

Citation: Kцlsch H. Polymorphisms in genes of proteins involved in cholesterol metabolism: evidence for Alzheimer's disease? Neurobiol Lipids Vol. 2, 2 (2 April 2003). Available at: http://neurobiologyoflipids.org/content/2/2/

Abstract: Cholesterol is suggested to be involved in the pathogenesis of Alzheimer's disease (AD). This commentary discusses the relevance of the polymorphisms in genes involved in cholesterol metabolism for the risk of AD, and explains why greater number of and larger studies are needed to provide solid evidence on whether such genes are involved in the pathogenesis of the disease.

Authors:Heike Kцlsch
Authors Institution: Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany; email: Heike.Koelsch[at]ukb.uni-bonn.de

Key words: view point; commentary; cholesterol homeostasis; 24S-hydroxycholesterol; 24S-hydroxylase; CYP46; HMG-CoA reductase; neurodegeneration; lipoprotein; apolipoprotein; ApoE4; lipids; LRP receptor; Lp(a); gene ploymorphism; ABCA1

A link between cholesterol, CNS, synapse and brain diseases: is there a need for a reinvention?

2004-11-15T13:01:00.000+02:00

Citation: Koudinov AR. A link between cholesterol, CNS, synapse and brain diseases: is there a need for a reinvention? Neurobiol Lipids Vol. 2, 1 (2 April 2003). Available at: http://neurobiologyoflipids.org/content/2/1/

Abstract: Since 1987 we know that "apolipoprotein E-containing lipoproteins may function to redistribute lipid and regulate cholesterol homeostasis within the brain". In 1993 we learned about the importance of "cholesterol synthesis and lipoprotein reuptake during synaptic remodeling". Over the past decade this knowledge was amassed (thanks to the pivotal contribution by many scientists) and elucidated the role for the failure of cholesterol homeostasis proper in neuronal degeneration. Still many questions remain. However, the statement that "a breakdown of cholesterol homeostasis may also play a role in neurodegenerative processes that have not been associated with this lipid so far" seems outdated.

Authors:Alexei R. Koudinov
Authors Institution: Russian Academy Med Sci, Moscow, Russian Federation, c/o P.O.Box 1665, Rehovot 76100 Israel, email: alexei[at]koudinov.info

Key words: cholesterol homeostasis; neurodegeneration; lipoprotein; apolipoprotein; LRP; Down's syndrome; ApoE4; electrophysiology; HMG CoA reductase; hippocampus; hippocampal slices; lipids; LDL; LDLR; VLDLR; LRP receptor; LTP; long term potentiation; lipid; Niemann Pick type C (NPC) disease; plasticity; memory

Editor's choice neurobiology of lipids sessions at Neuroscience 2004

2004-11-15T11:58:00.000+02:00

Citation: Editorial material. Editor's choice neurobiology of lipids sessions at Neuroscience 2004. Neurobiol Lipids Vol. 1, 9 (22 March 2004). Available at: http://neurobiologyoflipids.org/content/1/9/

Abstract: This article alerts interested readers about editors’ choice neurobiology of lipids sessions of the 32nd Society for Neuroscience (SfN) Annual Meeting, 2-7 November, 2002, Orlando, Fla. The article quotes original Neuroscience 2002 abstracts, provides the references for proceedings articles (published in Neurobiology of Lipids and elsewhere) and related bibliography. The entire collection of the neurobiology of lipids sessions at Neuroscience 2002 is available as earlier Neurobiology of Lipids publication ( 2002, Vol. 1, 5, http://neurobiologyoflipids.org/content/1/5 ).

Authors:Editorial material
Authors Institution: Neurobiology of Lipids, P.O.Box 1665 Rehovot 76100, Israel, sfnabstracts[at]neurobiologyoflipids.org

Key words: neuroscience of lipids; literature update; cholesterol; fatty acids; fa; srebp; lxr; phospholipids; lipoprotein; lipid peroxidation; psychiatry; neurology; receptor; amyloid hypothesis; Alzheimer's disease; Down syndrome; synapse; synaptic plasticity

Alzheimer's amyloid beta protein restores brain function: a central role for cholesterol?

2004-11-15T11:53:00.000+02:00

Citation: Koudinov AR, Koudinova NV. Amyloid beta protein restores hippocampal long term potentiation: a central role for cholesterol? Neurobiol Lipids Vol. 1, 8 (15 Sep 2003). Available at: http://neurobiologyoflipids.org/content/1/8/

Abstract: There is no understanding of the role of amyloid beta protein (Ab or Abeta) in brain function and Alzheimer's disease. In the present study we attempted to dissect out the role for Abeta in the synaptic plasticity in adult rat ex vivo hippocampal slices. The prolonged incubation of slices in our experimental setting preserved basic synaptic physiology but abrogated tetanus induced long term potentiation (LTP). Peptide Abeta1-40 rescued LTP while cholesterol synthesis inhibition abolished the restorative action of the peptide. Our observation confirms that Abeta protein is a functional player in cholesterol neurochemical pathways and in synaptic structure-functional plasticity. The finding also supports our proposed hypothesis that the change in Abeta biochemistry in Alzheimer's disease is a functional phenomenon aiming to compensate impaired cholesterol dynamics and associated neurotransmission and synaptic plasticity failure.

Authors:Alexei R. Koudinov and Natalia V. Koudinova
Authors Institution: Russian Academy of Medical Sciences, Moscow, Russian Federation, c/o P.O.Box 1665, Rehovot 76100 Israel, alexei[at]koudinov.info

Key words: Alzheimer's disease; amyloid precursor protein; APP; Down syndrome; etiology; lipids; learning; memory; long-term potentiation; LTP; LRP; neurodegeneration; oxidative stress; anti oxidation; PHF; NFT; tau; plaques; phospholipids; secretase; synapse; synaptic plasticity; SREBP; statins; Liver X LXR; sensor; presenilin

Abnormal cholesterol processing in Alzheimer's disease patient's fibroblasts

2004-11-15T11:50:00.000+02:00

Citation: Dufour F et al. Abnormal cholesterol processing in Alzheimer's disease patient's fibroblasts. Neurobiol Lipids Vol. 1, 7 (14 March 2003). Available at: http://neurobiologyoflipids.org/content/1/7/

Abstract: Cholesterol has recently received attention as a potentially important factor in Alzheimer's disease (AD) etiology. Caveolin, which binds cholesterol, plays a prominent role in cellular cholesterol transport. Here, we found a higher level of cholesterol and caveolin in the caveolae-enriched fractions prepared from AD patients' fibroblasts compared with age and sex matched controls (AC). Furthermore, the cross-linking activation of the prion protein, which is known to link to signal transduction of caveolin, is altered in AD fibroblasts. Our results suggest a dysregulation of cholesterol processing in AD fibroblasts which may contribute to the pathogenesis of AD.

Authors:Franck Dufour and colleagues
Authors Institution: Blanchette Rockefeller Neurosciences Institute, 9601 Medical Center Drive, Rockville, MD 20850, USA, fdufour[at]brni-jhu.org

Key words: Alzheimer's disease; amyloid beta precursor; APP; Down syndrome; etiology; lipids; lipoprotein; neurodegeneration marker; secretase; caveolin; caveolae; membrane; cell culture; human; non-neuronal tissue; neurodegenerative disease; signal transduction; prion; PKC; cross-linking; fractioning; biochemistry; triton

Amyloid beta, neural lipids, cholesterol and Alzheimer's disease

2004-11-15T11:46:00.000+02:00

Citation: Koudinova NV et al. Amyloid beta, neural lipids, cholesterol and Alzheimer's disease. Neurobiol Lipids Vol. 1, 6 (3 March 2003). Available at: http://neurobiologyoflipids.org/content/1/6/

Abstract: To date great number of articles were devoted to cholesterol (chol) but only few articles studied the role for chol in neuron function/degeneration. For decades this molecule had been known to be important for atherosclerosis and heart disease. First indication of the involvement of chol in Alzheimer disease (AD), however, come from the mid 1990s. At that time it was shown that heart disease patients develop brain deposits of amyloid beta (Ab or Abeta), a major dogmatic molecule of AD; that apoE (a chol transport apolipoprotein) allele e4 is a major genetic risk factor for AD; and that lab animals fed a chol diet express brain amyloid. These days it turns out that Abeta, long thought to be exclusively a pathologic protein, is a normal and functional apolipoprotein constituent of high density lipoproteins in plasma and CSF. Thus, we and others showed that Abeta modulates chol and phospholipid synthesis, and affects chol esterification. Protection of lipoproteins and other biomolecules from oxidation may represent another important function of Ab. We also discovered that neuronal chol homeostasis failure and the lack of chol supply to neurons by means of lipoprotein transport causes AD features, such as the failure of the neurotransmission and synaptic plasticity, degeneration of neuronal cell processes, and tau protein pathology.

Authors:Natalia V. Koudinova and colleagues
Authors Institution: Weizmann Institute of Science, Neurobiology/Biological Regulation, Candiotti Bldg, Rehovot 76100, Israel, nataliakoudinova[at]neurobiologyoflipids.org

Key words: Alzheimer's disease; amyloid beta precursor; APP; cytoskeleton; Down syndrome; etiology; lipids; learning; memory; lipoprotein; HDL; LDL; CSF; receptor; LTP; neurodegeneration marker; metal; oxidative stress; anti oxidation; PHF; NFT; tau phosphorylation; phospholipids; secretase; synaptic plasticity; SREBP; therapy; presenilin

32nd Society for Neuroscience annual meeting neurobiology of lipids sessions 2002

2004-11-15T11:00:00.000+02:00

Citation: Editorial Material. 32nd Society for Neuroscience annual meeting neurobiology of lipids sessions 2002. Neurobiol Lipids Vol. 1, 5 (23 Sep 2002). Available at: http://neurobiologyoflipids.org/content/1/5/

Abstract: 32nd Society for Neuroscience Neurobiology of Lipids sessions' article alerts interested readers about the abstracts on the journal scope that were presented at the 32nd Society for Neuroscience (SFN) annual meeting, 2-7 November, 2002 in Orlando, Fla. The abstracts were retrieved from the SFN web based abstract system as a result of the 'abstract text' search for the key words cholesterol, phospholipids, lipoprotein, fatty acids, lipid and lipid peroxidation. The reference to each abstract entry includes day/time, program number, presentation type, location, authors list, first author first affiliation, and the abstract title. Each abstract title provides link to abstract text at the www.scholarone.com web site. The presented list yielded editors' choice short list of eighteen noteworthy presentations. The short listed abstracts/presentations were invited to publish proceedings articles at the Neurobiology of Lipids.

Author: Editorial Material
Authors Institution: Neurobiology of Lipids, P.O.Box 1665 Rehovot 76100, Israel; sfnabstracts[at]neurobiologyoflipids.org

Key words: neuroscience of lipids; literature update; cholesterol; fatty acids; FA; SREBP; LXR; phospholipids; lipoprotein; lipid peroxidation; psychiatry; neurology

Cholesterol and Alzheimer's disease

2004-11-15T10:51:00.000+02:00

Citation: Wood GW et al. Cholesterol and Alzheimer's disease. Neurobiol Lipids Vol. 1, 3 (30 Aug 2002). Available at: http://neurobiologyoflipids.org/content/1/4/

Abstract: July 26, 2002 featured the conference "Cholesterol and Alzheimer's disease" held at the Biocenter, Frankfurt University, Frankfurt/Maine, Germany. The conference program included ten lectures and eight poster presentations on different aspects of the possible role for cholesterol in Alzheimer's disease and cholesterol neurobiology. This truly international round table event did not aim to come to the consensus but rather to summarize the advances and to discuss directions for near future development. This article presents the abstracts and related bibliography and aims to introduce readers to the multifarious subject of neural cholesterol with special emphasis on Alzheimer's disease and related disorders.

Authors: W. Gibson Wood and colleagues
Authors Institution: c/o Neurobiology of Lipids, P.O. Box 1665 Rehovot 76100, Israel; email: cholesterolandalzheimer[at]neurobiologyoflipids.org

Key words: treatment; cell biology; ABCA1; ApoE4; LRP; LDLR; apolipoprotein; phospholipid; amyloid beta precursor protein; alpha and beta secretase; aggregation and fibril formation; association study; PHF NFT tau phosphorylation; membrane fluidity; statin

The prion protein and cellular cholesterol homeostasis

2004-11-15T10:46:00.000+02:00

Citation: Diomede L et al. The prion protein and cellular cholesterol homeostasis. Neurobiol Lipids Vol. 1, 3 (30 Nov 2002). Available at: http://neurobiologyoflipids.org/content/1/3/

Abstract: The amount of lipids in cell membranes seems to regulate the interaction of the prion protein with cells and the propagation of prions. We investigated how the synthetic human prion peptide PrP 106-126 affected the chemico-physical and biochemical properties of nerve and HL60 cells. PrP 106-126 rapidly increased cell membrane microviscosity, inhibited cellular cholesterol release and increased membrane cholesterol content. PrP also inhibited cellular 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity. These findings indicate that PrP 106-126 alters cellular cholesterol homeostasis and may help clarify how changes in membrane lipid composition are involved in the progression of prion encephalopathies.

Authors: Luisa Diomede and colleagues
Authors Institution: Department of Molecular Biochemistry and Pharmacology and Department of Neurochemistry, Istituto di Ricerche Farmacologiche Mario Negri Via Eritrea 62, 20157 Milano, Italy; email: diomede[at]marionegri.it

Key words: Prion protein; PrP 106-126; 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase; membrane fluidity; cell homeoviscosity; etiology; lipids; learning; memory; lipoprotein; receptor; LTP; neurodegeneration marker; oxidative stress; PHF NFT tau phosphorylation; phospholipids; synaptic plasticity; disease; therapy; nutrition; cytoskeleton; Down syndrome; prions; scrapie