Modulation of beta-amyloid-related cognitive decline by brain-derived neurotrophic factor Val66Met polymorphism in preclinical Alzheimer's disease

Abstract

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has previously been implicated in Alzheimer's disease (AD)-related cognitive impairment. We aimed to determine whether BDNF Val66Met moderates A β amyloid-related cognitive decline, reduction in hippocampal volume, and A β amyloid accumulation in healthy older adults. Healthy older adults (n=165) enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study underwent positron emission tomography (PET) neuroimaging for Aβ amyloid using Pittsburgh Compound B (PiB), BDNF genotyping, and cognitive assessment at baseline, 18- and 36-months. Linear mixed models determined rates of change in cognition, hippocampal volume and A β amyloid accumulation over 36 months. In healthy older adults with high Aβ amyloid, Met carriers showed significant and moderate-to-large decline in episodic memory, executive function, and language, and greater reductions in hippocampal volume over 36 months compared to Val/Val homozygotes. BDNF Val66Met was unrelated to rates of change in cognition or hippocampal volume in participants with low Aβ amyloid. BDNF Val66Met was not associated with levels of Aβ amyloid in participants with high or low Aβ amyloid levels at baseline. Similarly, BDNF Val66Met was not associated with rates of Aβ amyloid accumulation in participants with high or low Aβ amyloid levels at baseline. BDNF Val66Met moderated the association between high A β amyloid and cognitive decline and hippocampal atrophy in healthy older adults. High A β amyloid levels coupled with Met carriage may be useful prognostic markers of accelerated cognitive decline and hippocampal degeneration in individuals in the preclinical stage of AD.