Nagarsheth Mehul H, Viehman Alex, Lippa Sara M, Lippa Carol F
Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
J Neurol Sci. 2006 May 15;244(1-2):111-6. doi: 10.1016/j.jns.2006.01.007. Epub 2006 Feb 13.
Notch-1 is a protein that influences cell fate decisions, with its expression occurring primarily during embryogenesis and development. However, Notch-1 is also expressed in the adult brain, in regions with high synaptic plasticity, particularly the hippocampus. Its role in adults is unknown; however, it may impact neurite outgrowth or cell differentiation in adult brain regions undergoing neurogenesis. Notch-1 is increased in Alzheimer's disease (AD); however, its expression in other CNS degenerative diseases has not been described. To begin to define the range of degenerative disorders where Notch-1 expression is altered, we examined Notch-1 immunoreactivity in a variety of neurodegenerative diseases to determine whether its increase is selective for AD. We examined sections of hippocampus from 13 AD, 13 classical Pick's disease (PiD; with Pick bodies), 4 dementia lacking distinctive histopathology (DLDH) and 8 control brains, emphasizing hippocampal (dentate gyrus) pathology. We determined that Notch-1 immunoexpression is increased in AD and PiD relative to control cases. DLDH cases were not significantly different than control cases with respect to Notch-1 expression. Given the increase in Notch-1 immunoexpression in AD and PiD, two diseases where abnormal tau aggregates are present, and the lack of Notch-1 immunoexpression in DLDH (where tau aggregates are absent), we cannot rule out the possibility that tau aggregates are associated with Notch-1 expression in neurodegenerative diseases.
Notch-1是一种影响细胞命运决定的蛋白质，其表达主要发生在胚胎发生和发育过程中。然而，Notch-1在成人大脑中也有表达，在具有高突触可塑性的区域，特别是海马体中。它在成人中的作用尚不清楚；然而，它可能会影响正在进行神经发生的成人大脑区域的神经突生长或细胞分化。Notch-1在阿尔茨海默病（AD）中增加；然而，其在其他中枢神经系统退行性疾病中的表达尚未见报道。为了开始确定Notch-1表达发生改变的退行性疾病范围，我们检查了多种神经退行性疾病中的Notch-1免疫反应性，以确定其增加是否对AD具有选择性。我们检查了13例AD、13例经典匹克病（PiD；有匹克小体）、4例缺乏特异性组织病理学的痴呆（DLDH）和8例对照大脑的海马体切片，重点关注海马体（齿状回）病理。我们确定，与对照病例相比，AD和PiD中的Notch-1免疫表达增加。DLDH病例在Notch-1表达方面与对照病例无显著差异。鉴于AD和PiD这两种存在异常tau聚集的疾病中Notch-1免疫表达增加，而DLDH（不存在tau聚集）中缺乏Notch-1免疫表达，我们不能排除tau聚集与神经退行性疾病中Notch-1表达相关的可能性。
