APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging
✍ Scribed by John C. Morris; Catherine M. Roe; Chengjie Xiong; Anne M. Fagan; Alison M. Goate; David M. Holtzman; Mark A. Mintun
- Book ID
- 101462678
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 326 KB
- Volume
- 67
- Category
- Article
- ISSN
- 0364-5134
No coin nor oath required. For personal study only.
✦ Synopsis
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 (A 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 A 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 A 42 with increased numbers of APOE4 alleles. Individuals with an APOE2 allele had no increase in MCBP with age and had higher CSF A 42 levels than individuals without an APOE2 allele. There was no APOE4 or APOE2 effect on CSF tau or ptau 181 . Interpretation: Increasing cerebral A deposition with age is the pathobiological phenotype of APOE4. The biomarker sequence that detects A deposition may first be lowered CSF A 42 , followed by elevated MCBP for PIB. A substantial proportion of cognitively normal individuals have presumptive preclinical AD.