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APOE predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Author(s) -
Morris John C.,
Roe Catherine M.,
Xiong Chengjie,
Fagan Anne M.,
Goate Alison M.,
Holtzman David M.,
Mintun Mark A.
Publication year - 2010
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21843
Subject(s) - apolipoprotein e , cerebrospinal fluid , medicine , allele , genotype , alzheimer's disease , pittsburgh compound b , pathology , endocrinology , biomarker , psychology , disease , biology , gene , genetics
Objective To examine interactions of apolipoprotein E ( APOE) genotype with age and with in vivo measures of preclinical Alzheimer disease (AD) in cognitively normal aging. Methods Two hundred forty‐one cognitively normal individuals, aged 45–88 years, had cerebral amyloid imaging studies with Pittsburgh Compound‐B (PIB). Of the 241 individuals, 168 (70%) also had cerebrospinal fluid (CSF) assays of amyloid‐beta 42 (Aβ 42 ), tau, and phosphorylated tau (ptau 181 ). All individuals were genotyped for APOE . Results The frequency of individuals with elevated mean cortical binding potential (MCBP) for PIB rose in an age‐dependent manner from 0% at ages 45–49 years to 30.3% at 80–88 years. Reduced levels of CSF Aβ 42 appeared to begin earlier (18.2% of those aged 45–49 years) and increase with age in higher frequencies (50% at age 80–88 years) than elevations of MCBP. There was a gene dose effect for the APOE4 genotype, with greater MCBP increases and greater reductions in CSF Aβ 42 with increased numbers of APOE4 alleles. Individuals with an APOE2 allele had no increase in MCBP with age and had higher CSF Aβ 42 levels than individuals without an APOE2 allele. There was no APOE4 or APOE2 effect on CSF tau or ptau 181 . Interpretation Increasing cerebral Aβ deposition with age is the pathobiological phenotype of APOE4 . The biomarker sequence that detects Aβ deposition may first be lowered CSF Aβ 42 , followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD. ANN NEUROL 2010;67:122–131