Abstract
ObjectiveCross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer’s disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ.MethodsThirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments.ResultsIn individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = −0.35, p = .401).ConclusionsAlthough preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.
Highlights
Current models of Alzheimer’s disease (AD) emphasise betaamyloid (Ab) as precipitating a cascade of events that result in synaptic loss and memory impairment [1]
Participants had undergone brain-derived neurotrophic factor (BDNF) genotyping at baseline, and positron emission tomography (PET) neuroimaging using Pittsburgh Compound B (PiB), structural magnetic resonance imaging (MRI), and neuropsychological assessment at baseline, 18 and 36 month follow-up (Table 1)
Relative to BDNFVal homozygotes, BDNFMet carriers showed a greater rate of decline in episodic memory and reduction in hippocampal volume over 36 months (Table 2, Figure 1a, 1b), with the effect size of difference between slopes for both measures, large in magnitude
Summary
Current models of Alzheimer’s disease (AD) emphasise betaamyloid (Ab) as precipitating a cascade of events that result in synaptic loss and memory impairment [1]. In humans, conclusions about the role of BDNF in AD have been based on the measurement of the effect of BDNF polymorphisms (e.g., Val66Met [rs6265]) on clinical or pathological features of the disease, or on risk for AD [3,4]. Evidence from such studies has been mixed with some showing BDNFMet carriers to have increased memory impairment, brain atrophy or risk of AD while others show that these same impairments are associated with BDNFVal homozygosity [3,4,7]
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