Nitsch R M, Rebeck G W, Deng M, Richardson U I, Tennis M, Schenk D B, Vigo-Pelfrey C, Lieberburg I, Wurtman R J, Hyman B T
Department of Neurology, Massachusetts General Hospital, Boston, USA.
Ann Neurol. 1995 Apr;37(4):512-8. doi: 10.1002/ana.410370414.
Alzheimer's disease (AD) is characterized by formation in brain of neurofibrillary tangles and of amyloid deposits. The major protein component of the former is tau, while the latter are composed of amyloid beta-peptides (A beta), which are derived by proteolytic cleavage of the amyloid beta-protein precursor (APP). Both tau and various secretory APP derivatives including A beta and APPS are present in human cerebrospinal fluid (CSF). To investigate whether clinical signs of AD are paralleled by changes in CSF levels of these proteins, we correlated quantitative measures of dementia severity with CSF concentrations of A beta, of APPS, and of tau. We found that levels of A beta in CSF of AD patients were inversely correlated both to cognitive and to functional measures of dementia severity. In contrast, levels of APPS and of tau did not correlate with dementia severity. Apolipoprotein E (apoE) genotype did not influence CSF levels of A beta, APPS, or tau, which were similar among AD patients with Apo E epsilon 3/3, epsilon 3/4, and epsilon 4/4 alleles. These data indicate that CSF levels of A beta decrease with advancing severity of dementia in AD and suggest that they are independent of a patient's Apo E genotype.
阿尔茨海默病（AD）的特征是大脑中出现神经原纤维缠结和淀粉样蛋白沉积。前者的主要蛋白质成分是tau蛋白，而后者则由淀粉样β肽（Aβ）组成，这些肽是由淀粉样β蛋白前体（APP）经蛋白水解切割产生的。tau蛋白以及包括Aβ和APPs在内的各种分泌型APP衍生物都存在于人的脑脊液（CSF）中。为了研究AD的临床症状是否与这些蛋白质的脑脊液水平变化相关，我们将痴呆严重程度的定量指标与脑脊液中Aβ、APPs和tau蛋白的浓度进行了关联分析。我们发现，AD患者脑脊液中Aβ的水平与痴呆严重程度的认知指标和功能指标均呈负相关。相比之下，APPs和tau蛋白的水平与痴呆严重程度无关。载脂蛋白E（apoE）基因型不影响脑脊液中Aβ、APPs或tau蛋白的水平，携带Apo E ε3/3、ε3/4和ε4/4等位基因的AD患者的这些蛋白水平相似。这些数据表明，AD患者脑脊液中Aβ的水平随着痴呆严重程度的加重而降低，并且提示它们与患者的Apo E基因型无关。
