Hock C, Golombowski S, Müller-Spahn F, Naser W, Beyreuther K, Mönning U, Schenk D, Vigo-Pelfrey C, Bush A M, Moir R, Tanzi R E, Growdon J H, Nitsch R M
Department of Psychiatry, University of Basel, Switzerland.
Eur Neurol. 1998;39(2):111-8. doi: 10.1159/000007917.
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive dementia that ultimately leads to death. Histopathological hallmarks of AD include brain amyloid deposits and neurofibrillary tangles. Major depression is a frequent diagnosis in every gerontopsychiatric clinic that sees patients with both cognitive and affective disorders. Many depressed patients, in fact, are clinically characterized by cognitive impairments. Thus, an assay that excludes - or confirms - probable AD in cognitively impaired patients is desirable. Such assays may use protein markers that are derived from such histopathologically relevant molecules as the amyloid precursor protein (APP) and its derivatives including the amyloid beta-peptides (Abeta). To evaluate the differential diagnostic properties of cerebrospinal fluid (CSF) Abeta and secreted soluble ectodomain (APPs), we quantitated CSF levels of these measures in AD patients and compared them to age-matched control patients with major depression. CSF levels of APPs and Abeta were similar in patients with AD or major depression, and the apolipoprotein E genotype had no influence on CSF levels of Abeta in AD patients. Measurement of Abeta peptide using a novel zinc/copper capture ELISA that detects aggregated Abeta peptides as well demonstrated similar levels in AD and major depression. In AD patients, CSF levels of total Abeta (Abeta1-40 plus Abeta1-42) were inversely correlated with a functional measure of dementia severity (NOSGER), suggesting that CSF levels of Abeta decrease with advancing severity of AD. Thus, CSF levels of Abeta are not useful for the differentiation of AD from major depression. However, CSF levels of Abeta reflect the severity of dementia and may be useful as biological markers of the stage of the disease.
阿尔茨海默病(AD)是最常见的神经退行性疾病,其特征为进行性痴呆,最终导致死亡。AD的组织病理学特征包括脑淀粉样蛋白沉积和神经原纤维缠结。重度抑郁症是每个老年精神科诊所常见的诊断结果,这些诊所会接待患有认知和情感障碍的患者。事实上,许多抑郁症患者在临床上表现为认知障碍。因此,需要一种检测方法来排除或确认认知障碍患者是否可能患有AD。此类检测方法可使用源自组织病理学相关分子的蛋白质标志物,如淀粉样前体蛋白(APP)及其衍生物,包括淀粉样β肽(Aβ)。为了评估脑脊液(CSF)Aβ和分泌型可溶性胞外域(APPs)的鉴别诊断特性,我们对AD患者脑脊液中这些指标的水平进行了定量,并将其与年龄匹配的重度抑郁症对照患者进行了比较。AD患者或重度抑郁症患者脑脊液中APPs和Aβ的水平相似,载脂蛋白E基因型对AD患者脑脊液中Aβ的水平没有影响。使用一种新型锌/铜捕获ELISA检测聚集的Aβ肽来测量Aβ肽,结果显示AD和重度抑郁症患者的水平也相似。在AD患者中,脑脊液中总Aβ(Aβ1-40加Aβ1-42)的水平与痴呆严重程度的功能指标(NOSGER)呈负相关,这表明脑脊液中Aβ的水平随着AD严重程度的增加而降低。因此,脑脊液中Aβ的水平对于区分AD和重度抑郁症并无帮助。然而,脑脊液中Aβ的水平反映了痴呆的严重程度,可能作为疾病阶段的生物学标志物。