Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts

Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and 11C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ1-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease.