The BDNF Val66Met Polymorphism as a Modifier of Early Tau Pathology in Sporadic Alzheimer’s Disease

Abnormal amyloid accumulation (Aβ+) represents the earliest biological event in Alzheimer’s disease (AD). However, rates of disease progression vary substantially among Aβ+ older adults. Allelic variation in the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (present in ~30% of the population) may account for some of this variability, with non-demented Aβ+ Met66 carriers demonstrating accelerated cognitive decline and neurodegeneration compared to matched Val66 homozygotes. However, the mechanisms underlying these effects are unclear. As tau pathology is more strongly associated with neuronal dysfunction than Aβ, this thesis examined whether BDNF Val66Met modifies vulnerability to pathological tau accumulation in non-demented Aβ+ older adults.