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

Anthony L. Hinrichs, Mark A. Mintun, Denise Head, Anne M. Fagan, David M. Holtzman, John C. Morris, Alison M. Goate

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background: To date, all known Alzheimer's disease genes influence amyloid beta (Aβ). Imaging of Aβ deposition in the human brain using Pittsburgh Compound B (PIB) offers the possibility of using cortical PIB binding as a quantitative endophenotype for genetic studies of late-onset Alzheimer's disease (LOAD). Methods: Heritability of Aβ deposition was determined using 82 elderly siblings from 35 families. Correlation with other Aβ related traits was determined using an unrelated sample of 112 individuals. For both samples, apolipoprotein E (APOE) ε4 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 ε4 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 (Aβ42) levels. Conclusions: These findings demonstrate that MCBP is a genetic trait and that other more easily measured Aβ related traits such as CSF Aβ42 do not fully explain the variance in MCBP. Thus, MCBP is a useful trait for large-scale genetic studies of LOAD.

Original languageEnglish
Pages (from-to)581-583
Number of pages3
JournalBiological Psychiatry
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2010

Keywords

  • Alzheimer's disease
  • PIB
  • genetics
  • imaging

Fingerprint

Dive into the research topics of 'Cortical Binding of Pittsburgh Compound B, an Endophenotype for Genetic Studies of Alzheimer's Disease'. Together they form a unique fingerprint.

Cite this