APOE predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging

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