Okonkwo Ozioma C, Mielke Michelle M, Griffith H Randall, Moghekar Abhay R, O'Brien Richard J, Shaw Leslie M, Trojanowski John Q, Albert Marilyn S
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Arch Neurol. 2011 Jan;68(1):113-9. doi: 10.1001/archneurol.2010.334.
To examine the effect of specific cerebrospinal fluid (CSF) profiles on the rate of cognitive decline, disease progression, and risk of conversion to Alzheimer disease (AD) dementia in patients with amnestic mild cognitive impairment (MCI).
Total tau (T-tau), tau phosphorylated at threonine 181, and β-amyloid 1-42 peptide (Aβ42) were immunoassayed in CSF samples obtained from patients with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative. Patients were then stratified by CSF profiles: (1) normal T-tau and normal Aβ42 (ie, normal-T-tauAβ42), (2) normal T-tau but abnormal Aβ42 (ie, abnormal-Aβ42), (3) abnormal T-tau but normal Aβ42 (ie, abnormal-T-tau), and (4) abnormal T-tau and abnormal Aβ42 (ie, abnormal-T-tauAβ42).
Fifty-eight sites in the United States and Canada.
One hundred ninety-five patients with MCI.
A composite cognitive measure, the Clinical Dementia Rating Scale-sum of boxes subscale, and conversion to AD dementia.
Patients with MCI with a CSF profile of abnormal-Aβ42 or abnormal-T-tauAβ42 experienced a faster rate of decline on the composite cognitive measure and the Clinical Dementia Rating Scale-sum of boxes subscale compared with those with normal-T-tauAβ42. They also had a greater risk of converting to AD dementia relative to the normal-T-tauAβ42 group. In contrast, those with a CSF profile of abnormal-T-tau did not differ from the normal-T-tauAβ42 group on any outcome. These findings were generally replicated when the sample was reclassified by patterns of tau phosphorylated at threonine 181 and Aβ42 abnormalities.
β-Amyloid abnormalities but not tau alterations are associated with cognitive deterioration, disease progression, and increased risk of conversion to AD dementia in patients with MCI. Patients with abnormal Aβ42 may be prime candidates for drug treatment and clinical trials in MCI.
研究特定脑脊液（CSF）指标对遗忘型轻度认知障碍（MCI）患者认知功能衰退速度、疾病进展以及转化为阿尔茨海默病（AD）痴呆症风险的影响。
对参与阿尔茨海默病神经影像倡议的MCI患者的脑脊液样本进行总tau蛋白（T-tau）、苏氨酸181位点磷酸化tau蛋白以及β淀粉样蛋白1-42肽（Aβ42）的免疫测定。然后根据脑脊液指标将患者分层：（1）T-tau正常且Aβ42正常（即正常-T-tauAβ42），（2）T-tau正常但Aβ42异常（即异常-Aβ42），（3）T-tau异常但Aβ42正常（即异常-T-tau），以及（4）T-tau异常且Aβ42异常（即异常-T-tauAβ42）。
美国和加拿大的58个研究点。
195例MCI患者。
综合认知测量、临床痴呆评定量表-方框总和子量表以及转化为AD痴呆症情况。
与正常-T-tauAβ42组相比，脑脊液指标为异常-Aβ42或异常-T-tauAβ42的MCI患者在综合认知测量和临床痴呆评定量表-方框总和子量表上的衰退速度更快。相对于正常-T-tauAβ42组，他们转化为AD痴呆症 的风险也更高。相比之下，脑脊液指标为异常-T-tau的患者在任何观察指标上与正常-T-tauAβ42组均无差异。当根据苏氨酸181位点磷酸化tau蛋白和Aβ42异常模式对样本重新分类时，这些结果总体上得到了重复。
β淀粉样蛋白异常而非tau蛋白改变与MCI患者的认知功能恶化、疾病进展以及转化为AD痴呆症的风险增加有关。Aβ42异常的患者可能是MCI药物治疗和临床试验的主要候选对象。
