Grey matter atrophy signatures and their genetic associations: a trans-disease study of Alzheimer's disease and multiple sclerosis.
- 1Department of Nuclear Medicine, Airport Hospital, Tianjin Medical University General Hospital, Tianjin, China.
- 2Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
Abstract
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. To map common and disease-specific grey matter (GM) atrophy patterns in AD and MS and identify their genetic correlations. 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. 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. 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.
Related
- Associations between different types of chronic lesions and gray matter atrophy in multiple sclerosis
- Circulating extracellular vesicle lipidomics identifies distinct signatures of amyotrophic lateral sclerosis and spinal muscular atrophy
- Resting-state cortical alpha frequency in Parkinson’s disease and multiple system atrophy: associations with diagnosis, age, and symptom burden
- Thalamic atrophy in active and inactive secondary progressive multiple sclerosis patients: A comparative study
- Domain-Specific Cognitive Associations With Standing Balance in Multiple Sclerosis
BibTeX
@article{zhao2026grey,
title = {{Grey matter atrophy signatures and their genetic associations: a trans-disease study of Alzheimer's disease and multiple sclerosis.}},
author = {Yunfei Zhao and Jie Sun and Busharemu Reheman and Xinyi Bai and Che Zhang and Wenyu Ding and Bohong Zou and Han Zhang and Zhang Zhang and Ningnannan Zhang},
journal = {Frontiers in neuroimaging},
year = {2026},
month = oct,
doi = {10.3389/fnimg.2026.1917609},
url = {https://europepmc.org/article/MED/42952837},
note = {CC BY},
}
RIS
TY - JOUR
TI - Grey matter atrophy signatures and their genetic associations: a trans-disease study of Alzheimer's disease and multiple sclerosis.
AU - Yunfei Zhao
AU - Jie Sun
AU - Busharemu Reheman
AU - Xinyi Bai
AU - Che Zhang
AU - Wenyu Ding
AU - Bohong Zou
AU - Han Zhang
AU - Zhang Zhang
AU - Ningnannan Zhang
PY - 2026
DA - 2026/10/14
JO - Frontiers in neuroimaging
DO - 10.3389/fnimg.2026.1917609
UR - https://europepmc.org/article/MED/42952837
AB - 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. To map common and disease-specific grey matter (GM) atrophy patterns in AD and MS and identify their genetic correlations. 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. 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. 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.
SN - 2813-1193
ER -