title: BDNF Val66Met, Aβ amyloid, and cognitive decline 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 the relationship between BDNF Val66Met and beta-amyloid (Aβ) on cognitive decline, hippocampal atrophy, and Aβ accumulation over 36 months in 165 healthy adults enrolled in the Australian Imaging, Biomarkers and Lifestyle study. In healthy adults with high Aβ, Met carriers showed significant and moderate-to-large declines in episodic memory, executive function, and language, and greater hippocampal atrophy over 36 months, compared with Val/Val homozygotes. BDNF Val66Met was not found to be related to rates of change in cognition or hippocampal volume in healthy adults with low Aβ. BDNF Val66Met did not relate to the amount of Aβ or to the rate of Aβ accumulation in either group. High Aβ 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.
authors.affiliation: Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia. y.lim@mhri.edu.au
authors.forename: Yen Ying
authors.initials: YY
authors.lastname: Lim
authors.forename: Victor L
authors.initials: VL
authors.lastname: Villemagne
authors.forename: Simon M
authors.initials: SM
authors.lastname: Laws
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Ellis
authors.forename: Karra D
authors.initials: KD
authors.lastname: Harrington
authors.forename: Pierrick
authors.initials: P
authors.lastname: Bourgeat
authors.forename: Olivier
authors.initials: O
authors.lastname: Salvado
authors.forename: David
authors.initials: D
authors.lastname: Darby
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Snyder
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Rowe
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
authors.forename: Paul
authors.initials: P
authors.lastname: Maruff
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001315:Australia; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D008715:Methionine / Q000235:genetics*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles; D014633:Valine / Q000235:genetics*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D019208:Brain-Derived Neurotrophic Factor; D013844:Thiazoles; D008715:Methionine; D014633:Valine
keywords: Aβ accumulation; BDNF Val66Met; Cognitive decline; Healthy older adults; Hippocampal atrophy; Preclinical Alzheimer's disease; beta-Amyloid