Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele.
Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele.
复制标题
老年痴呆与淀粉样蛋白血管病和 tau 血管周围病理相关，但与 APOE-epsilon4 等位基因纯合子患者的神经炎斑块无关。
DOI：
10.1007/s004010051186
复制
发表时间：
2000
影响因子：
12.7
通讯作者：
Ghetti,B
中科院分区：
文献类型：
--
作者：
Vidal,R;Calero,M;Piccardo,P;Farlow,MR;Unverzagt,FW;Méndez,E;Jiménez-Huete,A;Beavis,R;Gallo,G;Gomez-Tortosa,E;Ghiso,J;Hyman,BT;Frangione,B;Ghetti,B
β淀粉样蛋白沉积在皮层和小脑膜血管中，引起最常见的脑淀粉样血管病，见于散发性和家族性阿尔茨海默病（AD），是遗传性脑出血伴淀粉样变性（荷兰型）的主要特征。载脂蛋白E(APOE)- 4等位基因的存在被认为是阿尔茨海默病和阿尔茨海默病脑淀粉样血管病发展的危险因素。我们报告了两例apoe - 4纯合受试者的临床、病理和生化研究，他们患有老年痴呆，主要神经病理特征是严重的弥漫性淀粉样血管病伴血管周围tau神经原纤维病理。小脑膜血管、新皮层、海马、丘脑、小脑、中脑、脑桥、髓质的中小血管和毛细血管中均可见淀粉样蛋白β和ApoE的免疫反应性。免疫组化、氨基酸序列和质谱分析结果表明，β淀粉样蛋白的主要肽形式是残基Val40。血管周围持续出现tau免疫阳性细胞突起。淀粉样蛋白前体蛋白和早老素-1（PS-1）基因的DNA序列分析未发现突变。在这些apoe - 4纯合子患者中，病理过程与典型的AD患者不同，因为他们表现出与严重的β淀粉样蛋白血管病变、神经原纤维缠结、一些皮质路易体和缺乏神经斑块相关的血管周围tau免疫阳性细胞过程的沉重负担。这些病例强调了tau沉积可能与β淀粉样蛋白沉积在病理上相关的概念。
Amyloid β protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer’s disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of theApolipoprotein E(APOE)-ɛ4allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on twoAPOE-ɛ4homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid β protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid β protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of theAmyloid Precursor Proteingene andPresenilin-1(PS-1) gene revealed no mutations. In theseAPOE-ɛ4homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid β protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid β protein deposition.