Age-related change in the proportion of amyloid precursor protein mRNAs in the gray matter of cerebral cortex

Abstract

Alternative splicing of a transcript of amyloid precursor protein (APP) gene generates at least three types of mRNA coding for APP770, APP751, and APP695; the former two harbor, while the latter one lacks a Kunitz-type serine protease inhibitor (KPI). We compared, by using the RNase protection technique, APP mRNAs expression between gray and white matters in the frontal lobe, with special reference to Alzheimer's disease (AD) and aging. The proportions (y) of APP770 plus APP751 mRNAs in the white matter were nearly twice as much as those in the gray matter, both in control (non-AD) and AD brains; the difference between the two matters was statistically significant. Furthermore, in the gray matter of control, there was a positive correlation (y = 1.07x−57.1, r = 0.899) between the age (x) and the proportion (y), but not in the white matter where the proportion varied markedly among individuals. In AD brains, no significant correlation was found in either of the two matters. These results indicated that the APP mRNAs proportion in the gray matter may serve as a molecular index of the brain aging in non-AD persons.