Polygenic pathways shape white matter vulnerability to Alzheimer's disease-related pathophysiological changes.

ABSTRACT:

Background

The accumulation of amyloid-β_1-42 (Aβ_1-42) peptides and phosphorylated-Tau₁₈₁ (p-Tau₁₈₁) tangles from the preclinical stages of Alzheimer's disease (AD) has led to a biological definition of the disease. However, among Aβ_1-42-positive individuals, cognitive decline onset varies, and some never develop symptoms. Genetic influences on molecular pathways and their interactions with proteinopathy may underlie this heterogeneity. Leveraging data from a large sample of cognitively intact older adults in the European Prevention of Alzheimer Dementia (EPAD) cohort, we examined how AD-related pathophysiological changes (i.e., Aβ_1-42 and p-Tau₁₈₁), polygenic pathways and their interaction are associated w

SUBMITTER: Tranfa M 

PROVIDER: S-EPMC12604407 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature