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-beta (A beta) levels and change in relationship to APOE genotype, using 2 different measures of Ab in 2 different longitudinal cohorts. A beta accumulation was measured using positron emission tomography (PET) imaging and C-11-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) A beta(1-42) 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 A beta(1-42) declined longitudinally. APOE epsilon 4 was significantly associated with higher PET-PiB retention and lower CSF A beta(1-42), independent of age and sex, but APOE genotype did not significantly affect A beta change over time. APOE epsilon 4 carriers may be further along in the disease process, consistent with earlier brain A beta deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease. (C) 2015 Elsevier Inc. All rights reserved.