Cortical Binding of Pittsburgh Compound B, an Endophenotype for Genetic Studies of Alzheimer's Disease

Background: To date, all known Alzheimer's disease genes influence amyloid beta (A beta). Imaging of A beta deposition in the human brain using Pittsburgh Compound B (PIB) offers the possibility of using cortical FIB binding as a quantitative endophenotype for genetic studies of late-onset Alzheimer's disease (LOAD). Methods: Heritability of A beta deposition was determined using 82 elderly siblings from 35 families. Correlation with other A beta related traits was determined using an unrelated sample of 112 individuals. For both samples, apolipoprotein E (APOE) epsilon 4 was genotyped and positron emission tomography imaging was performed using the PIB ligand. Mean cortical binding potential (MCBP) was computed from several regions of interest. Results: MCBP has a high heritability (.61, p = .043). Furthermore, 74% of the heritable component cannot be explained by APOE epsilon 4 genotype. The unrelated sample reveals that a third of the variance of MCBP cannot be predicted by other biological traits, including cerebrospinal fluid (CSF) amyloid beta 42 (A beta 42) levels. Conclusions: These findings demonstrate that MCBP is a genetic trait and that other more easily measured A beta related traits such as CSF A beta 42 do not fully explain the variance in MCBP. Thus, MCBP is a useful trait for large-scale genetic studies of LOAD.