Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition

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Abstract
The presence of an APOE ϵ4 allele is the most established genetic risk factor for Alzheimer disease (AD), with a higher percentage of individuals with AD having an ϵ4 allele in comparison with the general population.1,2 In addition, the age at dementia onset is earlier,2,3 and the rate of cognitive decline may be higher in ϵ4 carriers with AD compared with noncarriers with AD.4-8 Even in cognitively normal middle-aged and older adults, APOE ϵ4 status has been associated with reduced cognitive performance9 and greater cognitive decline.10,11 More recently, it has been demonstrated that cognitively normal adults with an APOE ϵ4 allele show greater cortical amyloid deposition as indicated by increased binding of the amyloid imaging agent carbon 11–labeled Pittsburgh Compound B ([11C]PiB) and by lower levels of Aβ42 in cerebrospinal fluid (CSF) samples.12-15