Lack of allelic imbalance in APOE ε3/4 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 penetrance is due, in part, to an imbalance of allele expression in heterozygous individuals. In this regard, Lambert et at. (1998) reported that AD individuals have a higher APOE epsilon 4/total APOE ratio than non-demented control subjects. We tested this hypothesis using radioactive RT-PCR to quantitate APOE epsilon 3 and epsilon 4 allele expression levels in AD and non-AD brain samples from APOE epsilon 3/4 individuals. Quantitative analyses of amplified products within the linear range of amplification (18-20 cycles) revealed no difference from the expected 1:1 ratio in genomic DNA and in cDNA from AD and control brains. Using high PCR cycle numbers (similar to 30), we observed an artificial elevation of the APOE epsilon 3/total APOE ratio in both DNA and cDNA samples, possibly due to DNA heteroduplex formation. Our results 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.