In situ hybridization analysis of presenilin 1 mRNA in Alzheimer disease and in lesioned rat brain

Presenilin-1 (PS-1) gene mutations are responsible for the majority of the early onset familial forms of Alzheimer disease (AD), Neither PS-1's anatomic distribution in brain nor expression in AD have been reported, Using in situ hybridization in the rat forebrain, we show that PS-1 mRNA expression is primarily in cortical and hippocampal neurons, with less expression in subcortical structures, In a regional pattern similar to APP695, Excitotoxic lesions lead to loss of PS-1 signal, A neuronal pattern of expression of PS-1 mRNA was also observed in the human hippocampal formation, AD and control levels did not differ, PS-1 is expressed in brain areas vulnerable to AD changes more so than in areas spared in AD; however, PS-1 expression is not sufficient to mark vulnerable regions, Collectively, these data suggest that the neuropathogenic process consequent to PS-1 mutations begins in neuronal cell populations.