Lack of allelic imbalance in APOE epsilon 3/4 brain mRNA expression in Alzheimer's disease

Although the APOE epsilon 4 allele is a strong risk factor for Alzheimer's disease (AD), it is not deterministic, as many APOE epsilon 3/4 individuals do not develop AD. It has been hypothesized that this incomplete penetranc e is due, in part, to an imbalance of allele expression in heterozygous ind ividuals. In this regard, Lambert et at. (1998) reported that AD individual s have a higher APOE epsilon 4/total APOE ratio than non-demented control s ubjects. We tested this hypothesis using radioactive RT-PCR to quantitate A POE epsilon 3 and epsilon 4 allele expression levels in AD and non-AD brain samples from APOE epsilon 3/4 individuals. Quantitative analyses of amplif ied products within the linear range of amplification (18-20 cycles) reveal ed no difference from the expected 1:1 ratio in genomic DNA and in cDNA fro m AD and control brains. Using high PCR cycle numbers (similar to 30), we o bserved an artificial elevation of the APOE epsilon 3/total APOE ratio in b oth DNA and cDNA samples, possibly due to DNA heteroduplex formation. Our r esults do not support the hypothesis that allelic imbalance contributes to the risk of developing AD among APPE epsilon 3/4 heterozygote individuals. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.