Amyloid-ß burden and neuropsychological test performance in cognitively normal first-degree relatives at varying genetic risk for Alzheimer's disease

In Alzheimer's disease (AD) there is strong evidence that brain amyloid deposition precedes the emergence of dementia by many years. In addition, a greater accumulation of amyloid in the postmortem brain has been demonstrated in people who carry the major genetic risk factor for AD-APOE-e4. This study investigated the relationship between APOE e4 genotype, amyloid deposition, and neuropsychological test performance in pre-symptomatic individuals at varying genetic risk for AD. Cognitively normal subjects aged 50-69 with a first-degree family history for AD were genetically screened to select three groups: APOE genotype e4e4 (n = 14), e3e4 (n = 14), and e3e3 (n = 14), matched for age and sex. Subjects were then studied with C-11-labeled Pittsburgh Compound B ([C-11]PiB) PET, MRI, and neuropsychological testing. PET and MR images were co-registered for application of a ROI template (AAL for SPM2) to generate regional time-activity curves with cerebellum as reference region. Parametric BPND images were then generated using SRTM2 such that BPND = 0 reflected no specific binding. BPND was computed for a mean cortical ROI consisting of frontal, posterior cingulate-precuneus, lateral parietal, and lateral temporal ROIs. APOE-e4 carriers demonstrated significantly greater BPND (.17±.19) in comparison to non-carriers (.04±.09; F = 6.35, p = .016, ANCOVA controlling for age and sex), with no dosage effect between e4e4 (.19±.13) and e3e4 (.15±.23) groups. Significant cortical [C-11]PiB uptake was observed in APOE-e4 carriers throughout the age range studied (as young as age 51 in a e4e4 subject). There was no significant effect of APOE genotype on neuropsychological test performance. There were also no significant associations between mean cortical [C-11]PiB BPND and neuropsychological test performance in the overall sample.