Saito Yuko, Suzuki Kinuko, Nanba Eiji, Yamamoto Toshiyuki, Ohno Kousaku, Murayama Shigeo
Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Ann Neurol. 2002 Sep;52(3):351-5. doi: 10.1002/ana.10266.
Niemann-Pick type C disease is a neurovisceral storage disorder. Neurofibrillary tangles similar to those in Alzheimer's disease have been reported in most juvenile/adult patients without amyloid beta protein (Abeta) deposits. Recently, we found deposits of Abeta in the form of diffuse plaques in three (31- and 32-year-old sisters and a 37-year-old man) of nine Niemann-Pick type C disease patients, who presented with most severe tauopathy and with numerous neurofibrillary tangles. Abeta deposits were not detected in any of the control brains of patients younger than age 42 years. These three patients with Abeta deposit all were homozygotes of apolipoprotein E epsilon 4. Our study suggested that NPC1 gene mutations combined with homozygosity of apolipoprotein E epsilon 4 alleles could manifest neuropathology similar to that of Alzheimer's disease. Investigation of these patients may provide an important clue for understanding the pathogenesis of Alzheimer's disease.
尼曼-匹克C型病是一种神经内脏贮积症。在大多数无β淀粉样蛋白（Aβ）沉积的青少年/成年患者中，已报告存在与阿尔茨海默病中相似的神经原纤维缠结。最近，我们在9例尼曼-匹克C型病患者中的3例（31岁和32岁的姐妹以及一名37岁男性）中发现了弥漫性斑块形式的Aβ沉积，这些患者表现出最严重的tau蛋白病和大量神经原纤维缠结。在42岁以下患者的任何对照脑中均未检测到Aβ沉积。这3例有Aβ沉积的患者均为载脂蛋白Eε4纯合子。我们的研究表明，NPC1基因突变与载脂蛋白Eε4等位基因纯合性相结合可表现出与阿尔茨海默病相似的神经病理学特征。对这些患者的研究可能为理解阿尔茨海默病的发病机制提供重要线索。
