Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers
Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers
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DOI：
10.1002/ana.20639
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发表时间：
2005-11-01
影响因子：
11.2
通讯作者：
Grundke-Iqbal, I
中科院分区：
文献类型：
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作者：
Iqbal, K;Flory, M;Grundke-Iqbal, I
阿尔茨海默病是痴呆症最常见的原因，是多因素和异质性的;其诊断仍然是可能的。我们假设，一个以上的疾病机制产生阿尔茨海默氏病的组织病理学，和亚组的疾病可能会被确定的脑脊液（CSF）的蛋白质水平与老年（神经炎）斑块和神经纤维缠结。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CSF样本中的tau、泛素和A β（1-42）水平进行了免疫测定。潜谱分析根据这些分子标记物的水平将每个受试者分配到一个聚类。根据CSF中A β（1-42）、tau蛋白和泛素水平，阿尔茨海默病被细分为至少5个亚组;每个亚组表现出不同的临床特征。这些亚组可以通过CSF分析来识别，可能从不同的治疗药物中获得不同的益处。
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 A beta(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 A beta(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.