Work

Grey matter atrophy signatures and their genetic associations: a trans-disease study of Alzheimer’s disease and multiple sclerosis

Year: 2026

Type: review

Abstract: Background: Alzheimer's disease (AD) and multiple sclerosis (MS) share neuroimmune mechanisms that drive neurodegeneration. Current clinical interventions are largely confined to a single-disease approach, owing to the absence of trans-disease diagnostic markers and common therapeutic targets. Objective: To map common and disease-specific grey matter (GM) atrophy patterns in AD and MS and identify their genetic correlations. Methods: We performed a trans-disease meta-analysis in large-sample neuroimaging data from 2001 to 2024 (2,070 MS versus 1,625 healthy control, and 1,624 AD versus 1,607 healthy control) to map GM atrophy regions. The cross-sample partial least squares regression was applied to integrate gene expression profiles from the Allen Human Brain Atlas with region-specific GM atrophy patterns, achieving cross-scale analysis of identify neurodegeneration-associated genes. Results: MS-specific atrophy localized to the bilateral dorsomedial thalamic nucleus and precentral gyrus, whereas AD-specific atrophy centered on bilateral hippocampus-amygdala complex in age-unadjusted comparisons. The common atrophy patterns were found in the bilateral superior temporal gyrus, insulae, posterior cingulate cortex, amygdalae, and striatal components. We identified 834 genes whose spatial expression patterns were associated with the common GM atrophy pattern in AD and MS, including PLS2 + and PLS2- subsets, which encompass biological processes such as immunological homeostasis imbalance, cellular stress response, and neurometabolic/functional regulation. Conclusion: Findings establish shared cortical-limbic-striatal atrophy as pivotal neurodegeneration nexus in AD and MS. The identified gene-imaging signatures provide insights into potential pathway-specific mechanisms and may inform future therapeutic target discovery for dual-disease intervention.

Source: Frontiers in Neuroimaging

DOI: 10.3389/fnimg.2026.1917609