Cerebral small vessel disease and Alzheimer's disease susceptibility

Introduction: Individuals with Alzheimer's disease (AD) often also present with brain small vessel disease (cSVD). However, molecular pathways underlying the relationship between cSVD and AD phenotypes remain unclear.

Objective: We aim to identify genetic variants that contribute to the relationship between cSVD and AD biomarkers.

Study Design: We will conduct a novel genome-wide interaction study to identify the contribution of specific genes in the relationship between cSVD and AD biomarkers. We will also apply a candidate genes approach to explore properties of specific identified genes and genes with known biological relevance to cerebrovascular health and AD, in the NACC dataset. The relationship between the genetic variations and relevant biological phenotypes (e.g. specific brain volumetric measures, performance on cognitive assessments, fluid biomarkers, neuropathology, and other co-occurring neurodegenerative diseases, etc.) will be explored.

Significance: This study will allow us to investigate potential genetic predisposition which may increase the risk of developing AD biomarkers in individuals with extensive cSVD.

Individuals with Alzheimer’s disease (AD) often also have brain small vessel disease (SVD), where there are damages in the small blood vessels in their brain. However, the relationship between AD and SVD is not fully understood. This project aims to identify the genetic contribution to this relationship by looking at the relationships between genetic variations and imaging, and pathological markers of AD and SVD, as well as the impact of such genetic variations on gene and protein expression.