Prevalence of beta-amyloid plaques in a nondemented population using [11C]PIB and PET: Impact of APOE genotype

Background: Beta-amyloid plaque accumulation in the brain is a hallmark of Alzheimer's disease (AD) and likely precedes the clinical symptoms. Positron emission tomography (PET) with [11C]PIB allows in vivo visualization of beta-amyloid plaques. We used PET PIB to investigate the prevalence of beta-amyloid plaques in a nondemented sample and examined the impact of age and APOE genotype. Methods: Participants at the Washington University Alzheimer's Disease Research Center who had a Clinical Dementia Rating of 0 (nondemented) were recruited for PET [11C]PIB imaging. MRI-derived regions-of-interest of cerebellum (for nonspecific uptake reference), precuneus, gyrus rectus, lateral temporal cortex, and prefrontal cortex and Logan graphical analysis were used to estimate binding potential (BP). The BP values from these four regions were averaged to create the Mean Cortical BP, or MCBP. PET PIB results were examined as continuous and dichotomous variables: PIB+ (with MCBP > 0.18) or PIB- (MCBP < 0.18). Results: The nondemented participants (n = 242, M/F = 77/165), aged 45 to 89 years had a mean age of 67.0 y (SD = 10.7). Overall, 18.1% of participants were PIB+ and 34.2% were APOE ε4+. The likelihood of being PIB+ increased with age in years (OR = 1.10, 95%CI = 1.04-1.13, p< 0.0001), and with having an APOE ε4 allele (p<.0001; one APOE ε4 allele, OR = 6.73, 95%CI = 2.85-15.87, p < 0.0001; two APOE ε4 alleles, OR = 34.32, 95%CI = 6.43-183.23) in the adjusted logistic regression analyses. By decades the overall frequency of PIB+ was 6.0% for 50-59 y, 18.0% for 60-69 y, 26.2% for 70-79 y, and 30.3% for 80-89 y. When only APOE ε4 carriers were considered the prevalence of PIB+ scans were much higher reaching 47.4% for 70-79 yr and 71.4% for 80-89 y. Conclusions: Beta-amyloid plaque deposition by PET PIB imaging is seen to be present in a large subset of the nondemented elderly with high dependence on age and APOE status. Estimates of odds ratios with one or two APOE ε4 alleles were very high at 6.73 and 34.32, respectively, supporting the uniquely powerful influence of this genotype. However, it should be noted that 35% of all PIB+ scans occurred in participants with no APOE ε4 allele, indicating other factors must also be considered.