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eBook details

Title: Analysis of the Beta Amyloid Precursor Protein mRNAs in Alzheimer's Disease
Author : Todd Eliot Golde
Release Date : January 18, 2013
Genre: Medical,Books,Professional & Technical,
Pages : * pages
Size : 15358 KB

Description

Alzheimer's disease (AD) is a degenerative disorder of the central nervous system that results in a progressive loss of memory and higher cognitive function. In AD there are large numbers of senile plaques throughout the cerebral neocortex and hippocampus. Senile plaques consist of a spherical cluster of abnormal neurites surrounding an amyloid core. The major protein in the plaque core amyloid is a 39-42 amino acid polypeptide referred to as the β amyloid protein (βAP). Isolation of cDNAs encoding the βAP reveal that it is encoded as part of a larger protein referred to as the β amyloid precursor protein (βAPP). The βAPP gene produces several different mRNAs through alternative splicing. I have used both in situ hybridization and polymerase chain reaction (PCR) amplification of reverse transcribed RNA (referred to as PRT) to examine expression of the βAPP gene in AD. In the in situ hybridization studies I found that expression of the βAPP mRNA lacking a protease inhibitor domain (βAPP695) is selectively increased in AD neurons within the nucleus basalis of Meynert and locus ceruleus. Using PRT I have identified a novel alternatively spliced βAPP714 mRNA that is present at low abundance in each of the human brain regions, peripheral t issues, and cell lines that we have examined; demonstrated that non-neuronal cells in the human brain and meninges express βAPP mRNAs; and identified changes in βAPP gene expression that may contribute to amyloid deposition. These studies indicate that both increased expression and altered post-transcriptional processing of the βAPP may lead to generation of βAP and plaque formation in susceptible tissues. Finally I describe the modifications in the PRT technique that I have recently made. These modifications enable rapid and reliable quantitation of multiple RNAs in a single PCR reaction beginning with quantities of RNA as small as 0.1 μg. This modified PRT technique which I refer to as multiplex PRT, should be of great utility in mRNA phenotyping in the AD brain, especially in studies involving low copy number transcripts or in regional analysis where starting material is of limited supply.