Profiling of Differential Expression of Genes in Mice Carrying Both Mutant Presenilin 1 and Amyloid Precursor Protein Transgenes with or without Knockout of B Adrenergic Receptor Gene.

Alzheimer's disease (AD) is a lifelong progressive neurodegenerativa disease related with accumulation of amyloid β peptide (Aβ) produced by processing of amyloid precursor protein (APP) in the brain. In spite of several-decades effort on AD, there is still no medicine used to intervene with its pathological processes. Our previous studies made in transgenic animal models harboring familial AD genes of mutant presenilin 1 and amyloid precursor protein (APP) showed that βAR gene knock-out (βAR-KO) is beneficial in senile AD animals. Consistently, an epidemiological study lasted for two decades showed that the sole usage of β blockers as antihypertensive medicines is associated with fewer brain lesions and less brain shrinkage seen in senile AD patients. In order to understand why senile βAR-KO AD mice had better learning and memory, genomic effects of βAR-KO in the double transgenic AD mice were investigated. In the analysis, major genomic significance of βAR-KO was directed to influence protein-processing and presentation involving membrane structure and MHC class I and II protein complex, and lysosome and hydrolase activity for protein degradation, which are critical for accumulation of amyloid β peptide, the hallmark of AD.