Impact of APOE and BDNF Val66Met gene polymorphisms on cognitive functions in patients with amnestic mild cognitive impairment
Abstract
Apolipoprotein (APOE) ε4 is a well-known risk factor for late-onset Alzheimer disease (AD), but other AD-related gene polymorphisms might also be important, such as polymorphisms within the brain-derived neurotrophic factor (BDNF) gene. Carriage of BDNF Val66Met has been associated with faster cognitive decline and greater hippocampal atrophy in cognitively normal elderly.
We examined the effects of the concurrent presence of APOE and BDNF polymorphisms on cognitive functions and brain morphometry in amnestic mild cognitive impairment (aMCI) patients. 107 aMCI patients (mean age=72.2) were recruited from the Czech Brain Aging Study and based on APOE and BDNF genes polymorphisms were into 4 groups: ε4-BDNFVal/Val (n=37), ε4-BDNFMet (n=19), ε4+BDNFVal/Val (n=35), ε4+BDNFMet (n=16). All patients underwent clinical examination, magnetic resonance imaging and complex neuropsychological battery.
Among BDNFMet carriers, we observed that APOE 4+ carriers performed worse than APOE 3 homozygotes in immediate and delayed recall. There was no difference in memory performance associated with APOE variation in BDNFVal homozygotes.
We did not observe increased atrophy in areas related to memory function in the ε4+BDNFMet group. Our findings suggest that carriage of ε4+BDNFMet is associated with more pronounced memory dysfunction, which is typical feature for early AD, but not with structural brain changes in aMCI patients.
These findings suggest that in APOE ε4/BDNF Met carriers, synaptic dysfunction affecting memory may precede pronounced structural changes.