Changes in expression of lymphocyte amyloid precursor protein mRNA isoforms in normal aging and Alzheimer's disease

We measured, by employing a quantitative reverse-transcriptase PCR procedure, the relative (to beta-actin) levels of amyloid precursor protein APP(751) and APP(770) mRNA isoforms in lymphocytes obtained from 64 cognitively intact subjects ranging in ages from 20 to 91 years and in 19 patients with sporadic Alzheimer's disease. A positive correlation was observed between the relative lymphocyte APP(751) mRNA levels and subject age for the cognitively intact cohort. No difference in lymphocyte APP(751) mRNA levels was observed between Alzheimer's disease patients and their age-matched controls (> 55 years of age). However, the ratio of lymphocyte APP(751):APP(770) mRNA levels was significantly lower in Alzheimer's disease subjects compared to the > 55-year-old cohort. This decreased ratio is most likely due to an average 31% increase in the lymphocyte APP(770) isoform in Alzheimer's disease patients compared to 12% in the > 55-year-old cognitively intact group. Marked individual differences in amount of APP mRNA isoforms were encountered among all the subject groups and in the less than or equal to 55-year-old cohort, a 10-fold variation in individual APP(751) mRNA levels was observed. The relevance of these findings in lymphocytes to the pathogenesis of Alzheimer's disease is discussed.