Alzheimer's disease-related gene expression in the brain of senescence accelerated mouse

The levels of Alzheimer's disease (AD)-related genes, including beta-amyloi d precursor protein(APP), presenilin-1 (PS-1), PS-2, apoE, tau, c-fos, neur al cell adhesion molecular 180 (NCAM-180), TGF-beta 1, IL-1 alpha/beta, IL- 6, TNF-alpha/beta, alpha-2-Macroglobulin (alpha 2M), class II major histoco mpatibility antigen la (MHCII la), bcl-2 alpha, glucocorticoid receptor-alp ha (GR alpha) and mineralocorticold receptor (MR) mRNAs were determined by reverse transcription polymerase chain reaction (RT-PCR) in the hippocampus and cerebral cortex of senescence accelerated mouse (SAM). The levels of T GF-beta 1, IL-1 alpha, TNF-beta, c-fos, NCAM-180, PS-1 and APP mRNAs were n ormally expressed in SAMP8 compared with age-matched other subline that is resistant (SAMR1). The levels of apoE, GR alpha and MR mRNAs in the hippoca mpus of SAMP8, especially GR alpha, were evidently lower than those in the hippocampus of SAMR1. While bcl-2 alpha, PS-2 and tau mRNA levels of SAMP8 were significantly higher than those of SAMR1. Inflammatory cytokines (IL-1 beta, IL-6, TNF-alpha), alpha 2M and MHCII la antigen mRNAs were not detec ted in the brain of SAM. The differences of gene expression in the cerebral cortex were less evident than in the hippocampus. The results indicated th at some genes abnormally expressed in the AD brain were also found in the b rain of SAMP8, which may contribute to its age-related deterioration of lea rning and memory. Our results also suggested that functional and pathologic al changes which occurred in the brain of SAMP8 possessed some different as pects in comparison with the AD in consideration of the differences in gene expression. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.