Aside from
apolipoprotein E (
APOE), genetic risk factors for β
amyloid deposition in cognitively intact individuals remain to be identified.
Brain derived neurotrophic factor (
BDNF) modulates neural plasticity, which has been implicated in
Alzheimer's disease. We examined in cognitively normal older adults whether the
BDNF codon 66 polymorphism affects β
amyloid burden and the relationship between β
amyloid burden and cognitive scores, and how this relates to the effect of
APOE.
Amyloid load was measured by means of (18)F-flutemetamol PET in 64 community-recruited cognitively intact individuals (mean age 66, S.D. 5.1). Recruitment was stratified according to a factorial design with
APOE (ε4 allele present vs absent) and
BDNF (met allele at
codon 66 present vs absent) as factors. Individuals in the four resulting cells were matched by the number of cases, age, and gender. Among the
APOE ε4 carriers,
BDNF met positive subjects had a significantly higher
amyloid load than
BDNF met negative subjects, while
BDNF met carrier status did not have an effect in
APOE ε4 noncarriers. This interaction effect was localized to precuneus, orbitofrontal cortex, gyrus rectus, and lateral prefrontal cortex. In the
APOE ε4/
BDNF met carriers, a significant inverse relationship existed between episodic memory scores and
amyloid burden but not in any of the other groups. This hypothesis-generating experiment highlights a potential role of
BDNF polymorphisms in the preclinical phase of β
amyloid deposition and also suggests that
BDNF codon 66 polymorphisms may influence resilience against β
amyloid-related effects on cognition.