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 (Abeta). Imaging of Abeta 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 Abeta deposition was determined using 82 elderly siblings from 35 families. Correlation with other Abeta related traits was determined using an unrelated sample of 112 individuals. For both samples, apolipoprotein E (APOE) epsilon4 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 epsilon4 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 (Abeta42) levels.


CONCLUSIONS
These findings demonstrate that MCBP is a genetic trait and that other more easily measured Abeta related traits such as CSF Abeta42 do not fully explain the variance in MCBP. Thus, MCBP is a useful trait for large-scale genetic studies of LOAD.
Hinrichs
Anthony L
AL
Department of Psychiatry, Washington University School of Medicine, St. Louis, Misouri, USA. tony@fire.wustl.edu
Mintun
Mark A
MA
Head
Denise
D
Fagan
Anne M
AM
Holtzman
David M
DM
Morris
John C
JC
Goate
Alison M
AM
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D005192:Family Health; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles; D016875:tau Proteins / Q000134:cerebrospinal fluid
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D002250:Carbon Radioisotopes; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); D016875:tau Proteins