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Original Article
APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging
Article first published online: 21 AUG 2009
DOI: 10.1002/ana.21843
Copyright © 2010 American Neurological Association
Additional Information
How to Cite
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M. and Mintun, M. A. (2010), APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann Neurol., 67: 122–131. doi: 10.1002/ana.21843
Publication History
- Issue published online: 23 FEB 2010
- Article first published online: 21 AUG 2009
- Accepted manuscript online: 21 AUG 2009 12:00AM EST
- Manuscript Revised: 1 JUL 2009
- Manuscript Accepted: 1 JUL 2009
- Manuscript Received: 23 APR 2009
Funded by
- National Institute on Aging. Grant Numbers: P50 AG05681, P01 AG03991, P01 AG026276
- Charles and Joanne Knight Alzheimer Research Initiative of the Washington University Alzheimer's Disease Research Center, St. Louis, MO
- National Center for Research Resources. Grant Number: Postdoctoral Program of 1UL1RR024992-01
Abstract
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-beta42 (Aβ42), tau, and phosphorylated tau (ptau181). 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 Aβ42 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 Aβ42 with increased numbers of APOE4 alleles. Individuals with an APOE2 allele had no increase in MCBP with age and had higher CSF Aβ42 levels than individuals without an APOE2 allele. There was no APOE4 or APOE2 effect on CSF tau or ptau181.
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 Aβ42, followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD. ANN NEUROL 2010;67:122–131