Genome-Wide Association Studies of Alzheimer's Disease Biomarkers in Adults with Down Syndrome

Individuals with Down syndrome (DS) are at an increased risk of Alzheimer’s disease (AD) due to overexpression of APP on chromosome 21. Recently, neuroimaging and blood-based biomarkers have been used to quantify tau burden and Aβ protein levels, and differences in these biomarkers are associated with clinical progression of AD. In this study I conducted genome wide association studies to identify significant variants within eight biomarkers derived from single molecule arrays (SIMOA) of plasma and position emission tomography (PET) scans: (1) tau PET, (2) centiloid, (3) Aβ40, (4) Aβ42, (5) Aβ42:Aβ40 ratio, (6) p- tau181, (7) p-tau217, and (8) total p-tau. The genome wide association studies were conducted using PLINK for chromosomes 1–20 and 22 and using Matrix eQTL for chromosome 21, to account for the trisomy. Four of the biomarkers had genome-wide significant variants: centiloid, Aβ40, Aβ42, and Aβ42:Aβ40 ratio. These genome-wide significant variants were near ATB8B3 (Aβ42), ADAMTS9 (centiloid), PARVA (centiloid), AC023347.1 (Aβ40), and AC018685.2 (Aβ42:Aβ40). Currently there are limited treatments and no known cures for Alzheimer’s disease. Genes identified in this study should be investigated further to see if there are possible applications of these genes in risk assessment or prevention, especially for this at-risk population.