Delacourte A, David J P, Sergeant N, Buée L, Wattez A, Vermersch P, Ghozali F, Fallet-Bianco C, Pasquier F, Lebert F, Petit H, Di Menza C
Unité INSERM 422, Lille, France.
Neurology. 1999 Apr 12;52(6):1158-65. doi: 10.1212/wnl.52.6.1158.
To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and the different stages of AD.
The pathophysiologic significance of AD lesions, namely amyloid plaques and neurofibrillary tangles, is still unclear, especially their interrelationship and their link with cognitive impairment.
The study included 130 patients of various ages and different cognitive statuses, from nondemented control subjects (n = 60, prospective study) to patients with severe definite AD. Paired helical filaments (PHF)-tau and Abeta were used as biochemical and histologic markers of NFD and amyloid plaques, respectively.
NFD with PHF-tau was systematically present in variable amounts in the hippocampal region of nondemented patients age >75 years. When NFD was found in other brain areas, it was always along a stereotyped, sequential, hierarchical pathway. The progression was categorized into 10 stages according to the brain regions affected: transentorhinal cortex (S1), entorhinal (S2), hippocampus (S3), anterior temporal cortex (S4), inferior temporal cortex (S5), medium temporal cortex (S6), polymodal association areas (prefrontal, parietal inferior, temporal superior) (S7), unimodal areas (S8), primary motor (S9a) or sensory (S9b, S9c) areas, and all neocortical areas (S10). Up to stage 6, the disease could be asymptomatic. In all cases studied here, stage 7 individuals with two polymodal association areas affected by tau pathologic states were cognitively impaired.
The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.
确定正常衰老及阿尔茨海默病（AD）不同阶段神经纤维变性（NFD）的时空图谱。
AD病变即淀粉样斑块和神经原纤维缠结的病理生理意义仍不明确，尤其是它们之间的相互关系以及与认知障碍的联系。
该研究纳入了130名不同年龄和认知状态的患者，从非痴呆对照受试者（n = 60，前瞻性研究）到重度确诊AD患者。成对螺旋丝（PHF）-tau和β淀粉样蛋白（Aβ）分别用作NFD和淀粉样斑块的生化及组织学标志物。
年龄>75岁的非痴呆患者海马区中系统性存在不同数量的伴有PHF-tau的NFD。当在其他脑区发现NFD时，其总是沿着固定的、连续的、分层的路径发展。根据受影响的脑区将进展分为10个阶段：内嗅皮质过渡区（S1）、内嗅区（S2）、海马体（S3）、颞叶前皮质（S4）、颞叶下皮质（S5）、颞叶中皮质（S6）、多模式联合区（前额叶、顶叶下部、颞叶上部）（S7）、单模式区（S8）、初级运动区（S9a）或感觉区（S9b、S9c）以及所有新皮质区（S10）。到第6阶段，疾病可能无症状。在此研究的所有病例中，有两个多模式联合区受tau病理状态影响的第7阶段个体存在认知障碍。
记录了NFD与阿尔茨海默型痴呆之间的关系以及AD的生化诊断标准，并显示了AD与特定脑区NFD程度之间的关联。
