title: Polymorphism of brain derived neurotrophic factor influences β amyloid load in cognitively intact apolipoprotein E ε4 carriers.
abstract: 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.
authors.affiliation: Laboratory for Cognitive Neurology, University of Leuven, Belgium ; Alzheimer Research Centre KU Leuven, Leuven Institute for Neuroscience and Disease, Belgium.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Adamczuk
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: De Weer
authors.forename: Natalie
authors.initials: N
authors.lastname: Nelissen
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Kristel
authors.initials: K
authors.lastname: Sleegers
authors.forename: Karolien
authors.initials: K
authors.lastname: Bettens
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vandenbulcke
authors.forename: Pradeep
authors.initials: P
authors.lastname: Thiyyagura
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
keywords: AD, Alzheimer's disease; APOE; APOE, apolipoprotein E; Alzheimer; Amyloid PET; BDNF; BDNF, brain-derived neurotrophic factor; Flutemetamol; MRI, magnetic resonance imaging; PET, positron emission tomography; PVC, partial volume correction; SUVR, standardized uptake value ratio; SUVRcomp, SUVR in composite cortical volume of interest; VOI, volume-of-interest; met, methionine; val, valine