Iqbal Khalid, Flory Michael, Khatoon Sabiha, Soininen Hilkka, Pirttila Tuula, Lehtovirta Maarit, Alafuzoff Irina, Blennow Kaj, Andreasen Niels, Vanmechelen Eugeen, Grundke-Iqbal Inge
New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Ann Neurol. 2005 Nov;58(5):748-57. doi: 10.1002/ana.20639.
Alzheimer's disease, the most common cause of dementia, is multifactorial and heterogeneous; its diagnosis remains probable. We postulated that more than one disease mechanism yielded Alzheimer's histopathology, and that subgroups of the disease might be identified by the cerebrospinal fluid (CSF) levels of proteins associated with senile (neuritic) plaques and neurofibrillary tangles. We immunoassayed levels of tau, ubiquitin, and Abeta(1-42) in retrospectively collected CSF samples of 468 clinically diagnosed Alzheimer's disease patients (N = 353) or non-Alzheimer's subjects (N = 115). Latent profile analysis assigned each subject to a cluster based on the levels of these molecular markers. Alzheimer's disease was subdivided into at least five subgroups based on CSF levels of Abeta(1-42), tau, and ubiquitin; each subgroup presented a different clinical profile. These subgroups, which can be identified by CSF analysis, might benefit differently from different therapeutic drugs.
阿尔茨海默病是痴呆最常见的病因，具有多因素性和异质性；其诊断仍具有可能性。我们推测，不止一种疾病机制导致了阿尔茨海默病的组织病理学表现，并且该疾病的亚组可能通过与老年（神经炎性）斑块和神经原纤维缠结相关的蛋白质的脑脊液（CSF）水平来识别。我们对468例临床诊断为阿尔茨海默病患者（N = 353）或非阿尔茨海默病受试者（N = 115）的回顾性收集的脑脊液样本中的tau、泛素和β淀粉样蛋白1-42（Aβ(1-42)）水平进行了免疫测定。潜在类别分析根据这些分子标志物的水平将每个受试者分配到一个类别中。基于脑脊液中Aβ(1-42)、tau和泛素的水平，阿尔茨海默病至少被分为五个亚组；每个亚组呈现出不同的临床特征。这些可通过脑脊液分析识别的亚组，可能从不同的治疗药物中获得不同的益处。
