Apolipoprotein E genotype and deposits of Abeta40 and Abeta42 in Alzheimer disease.

OBJECTIVE: To examine the differential deposition of amyloid beta (Abeta) peptide isoforms Abeta40 and Abeta42 in the Alzheimer disease (AD) brain in relation to the apolipoprotein E (APOE) genotype.

BACKGROUND: The APOE epsilon4 genotype is an inherited risk factor for AD and is associated with increased deposition of Abeta protein in the cerebral cortex. Previous data from familial AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein suggest that the long form of Abeta peptide, Abeta42, is selectively increased in these circumstances. Herein, we examine whether APOE genotype influenced the species of Abeta peptide deposited.

DESIGN AND METHODS: The amount of Abeta40, Abeta42, and total Abeta deposited in immunostained temporal lobe tissue of 28 cases of AD of known APOE genotype was determined.

RESULTS: Individuals with the APOE epsilon4 genotype (APOE epsilon4/4) were associated with both increased Abeta40 (P<.05) and Abeta42 (P<.05) compared with individuals without the APOE epsilon4/4 genotype.

CONCLUSION: Our results differ from the data from AD due to mutations in presenilin 1 and presenilin 2 genes and the amyloid precursor protein and suggest that the APOE epsilon4 genotype mediates increased Abeta deposition by a mechanism that differs from that found in other genetic causes of AD.