Expression of beta-secretase mRNA in transgenic Tg2576 mouse brain with Alzheimer plaque pathology

On the basis of the recent cloning of the beta-secretase, the beta-site amy loid precursor protein (APP)-cleaving enzyme (BACE), (Science, 286 (1999) 7 35), digoxigenin-labelled riboprobes were generated to localize the cellula r expression pattern of BACE mRNA in brain sections of transgenic Tg2576 mi ce, overexpressing the Swedish mutation of the APP695 isoform, Non-radioact ive in situ hybridization in combination with immunohistochemistry to ident ify the cell types and beta-amyloid deposits revealed strong BACE mRNA hybr idization signals in neurons of the cerebral cortex, hippocampal formation, thalamus and cholinergic basal forebrain nuclei, while astrocytes did not display any labeling. Neurons surrounding beta-amyloid deposits did not dem onstrate altered expression level of BACE mRNA as compared to neurons in co rtical areas that are free of beta-amyloid deposits, and the regional expre ssion pattern of BACE mRNA did not correlate with the distribution of beta- amyloid deposits. These data suggest that high level of expression of BACE mRNA is not necessarily related to enhanced deposition of beta-amyloid plaq ues. To elucidate those facto rs that contribute to beta-amyloid plaque dep osition in a particular region, the transgenic Tg2576 mouse may represent a n appropriate tool. (C) 2000 Elsevier Science Ireland Ltd. All rights reser ved.