Spatial transcriptomic patterns underlying amyloid-ß and tau pathology are associated with cognitive dysfunction in Alzheimer's disease.
Cell Rep
; 43(2): 113691, 2024 Feb 27.
Article
in En
| MEDLINE
| ID: mdl-38244198
ABSTRACT
Amyloid-ß (Aß) and tau proteins accumulate within distinct neuronal systems in Alzheimer's disease (AD). Although it is not clear why certain brain regions are more vulnerable to Aß and tau pathologies than others, gene expression may play a role. We study the association between brain-wide gene expression profiles and regional vulnerability to Aß (gene-to-Aß associations) and tau (gene-to-tau associations) pathologies by leveraging two large independent AD cohorts. We identify AD susceptibility genes and gene modules in a gene co-expression network with expression profiles specifically related to regional vulnerability to Aß and tau pathologies in AD. In addition, we identify distinct biochemical pathways associated with the gene-to-Aß and the gene-to-tau associations. These findings may explain the discordance between regional Aß and tau pathologies. Finally, we propose an analytic framework, linking the identified gene-to-pathology associations to cognitive dysfunction in AD at the individual level, suggesting potential clinical implication of the gene-to-pathology associations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
/
Cognitive Dysfunction
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2024
Document type:
Article