Page K, Hollister R, Tanzi R E, Hyman B T
Laboratory of Genetics and Aging, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14020-4. doi: 10.1073/pnas.93.24.14020.
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.
早老素-1（PS-1）基因突变是大多数早发性家族性阿尔茨海默病（AD）的病因。PS-1在脑中的解剖分布及其在AD中的表达均未见报道。通过对大鼠前脑进行原位杂交，我们发现PS-1 mRNA表达主要位于皮质和海马神经元，在皮质下结构中的表达较少，其区域分布模式与APP695相似。兴奋性毒性损伤导致PS-1信号丧失。在人类海马结构中也观察到PS-1 mRNA的神经元表达模式。AD组和对照组的表达水平没有差异。PS-1在易发生AD病变的脑区中的表达比在AD未累及区域中的表达更多；然而，PS-1表达不足以标记易损区域。总体而言，这些数据表明PS-1突变导致的神经致病过程始于神经元细胞群体。
