Nature Neuroscience

Foamy microglia link oxylipins to disease progression in multiple sclerosis

Daan van der Vliet — 2026-05-21

Nature Neuroscience, Published online: 21 May 2026; doi:10.1038/s41593-026-02302-3

Foamy microglia are associated with multiple sclerosis progression, linking phagocytosis, altered lipid metabolism (oxylipins) and lysosomal stress to nonclassical neuroinflammation and disease severity, highlighting potential therapeutic targets.

Considering biological limitations of lesion network mapping

Lorenzo Pini — 2026-05-20

Nature Neuroscience, Published online: 20 May 2026; doi:10.1038/s41593-026-02319-8

Lesion network mapping (LNM), or atrophy network mapping, has become a widely adopted tool for linking focal brain lesions or neurodegenerative brain clusters, respectively, to distributed functional networks associated with cognitive or clinical deficits. Recent insights, however, suggest that LNM primarily captures elementary topological properties of the normative connectome rather than disorder-specific circuits. Independent clinical evidence supports these methodological concerns, reflecting a deeper biological issue. LNM is inherently unable to capture the higher-order disconnection effects and non-linear connectivity changes that characterize the brain response to a broad range of neurological conditions. Brain injuries can induce widespread changes in distal regions not directly affected by the damage, as well as complex patterns of pathological hyperconnectivity and hypoconnectivity that evolve over time and whose functional significance remains uncertain. These phenomena represent a central challenge in clinical neuroscience. LNM is intrinsically limited in capturing these dynamics, with important implications for clinical translation and neuromodulation.

Tau aggregates cause reactivation of transposable DNA elements, leading to Z-RNA–ZBP1-mediated neuronal death

Wei Liu — 2026-05-20

Nature Neuroscience, Published online: 20 May 2026; doi:10.1038/s41593-026-02299-9

Tau aggregates disrupt heterochromatin by sequestering H3K9me3, reactivating transposable elements. This generates Z-RNAs, activating ZBP1 to drive neuronal death. ZBP1 haploinsufficiency reverses cognitive decline in aged tau mice, offering a therapeutic target for tauopathies.

Spatial proteomic analysis in human Alzheimer’s disease brains enables identification of microenvironment-dependent microglial cell states

Paula Sanchez-Molina — 2026-05-18

Nature Neuroscience, Published online: 18 May 2026; doi:10.1038/s41593-026-02267-3

Myeloid cells show marked heterogeneity in Alzheimer’s disease. This study introduces CODEX-CNS, a single-cell spatial proteomics pipeline, and identifies a human microglial subpopulation enriched in Alzheimer’s disease brains that associates with dense amyloid-β plaques.

Parsing autism spectrum heterogeneity through fMRI

Tatiana A. Shnitko — 2026-05-15

Nature Neuroscience, Published online: 15 May 2026; doi:10.1038/s41593-026-02269-1

Autism is remarkably heterogeneous, posing a long-standing challenge for linking genetics to brain dynamics. A cross-species study identifies two principal dysconnectivity signatures across 20 mouse models of autism risk, each associated with distinct molecular pathways, and shows analogous connectivity patterns in autistic humans. These results establish a translational framework for biologically grounded fMRI phenotyping.

Excitatory synapses onto axonic spines jump-start action potentials and route information flow

Hongkun Yang — 2026-05-15

Nature Neuroscience, Published online: 15 May 2026; doi:10.1038/s41593-026-02282-4

The axon initial segment was known to receive GABAergic synaptic inputs. Yang et al. show that it can be excited directly via specialized ‘axonic spines’. These spines thus boost neuronal firing and act as a fast track to route circuit information.

Autism subtypes identified using cross-species functional connectivity analyses

Marco Pagani — 2026-05-15

Nature Neuroscience, Published online: 15 May 2026; doi:10.1038/s41593-026-02287-z

Pagani et al. used cross-species fMRI to reveal two autism subtypes, characterized by lower and higher brain connectivity and linked to synaptic and immune-related pathways, respectively.

Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming

Ziyang Zhang — 2026-05-14

Nature Neuroscience, Published online: 14 May 2026; doi:10.1038/s41593-026-02300-5

This study reveals that the immune system has a role in driving ALS. These findings link blood immune changes to spinal cord damage and suggest personalized treatments targeting specific immune pathways.