Arch Neurol：探究与阿尔茨海默氏症有关的蛋白质

一项针对脑脊液蛋白与阿尔茨海默病相关的临床症状与认知正常的老年患者之间的关系的研究表明：β-淀粉样蛋白相关的临床病理的下降与P-tau蛋白磷酸化的tau蛋白升高有联系，相关研究论文发表在Archives of Neurology杂志上。

加州圣地亚哥医学院的大学Rahul S. Desikan医学博士和同事评估了107阿尔茨海默氏病患者个体。他们检查脑脊液（CSF）的tau蛋白181的磷酸化（P-tau蛋白181p）和脑脊液Αβ1-42的水平。

结果表明脑脊液Αβ1-42的减少与脑脊液P-tau蛋白181p的升高之间有显著联系。

这些研究发现与以前的研究结果相一致，我们的结果表明临床上正常的老年个体本身Αβ沉积并不与临床病理特征下降有关，P-tau蛋白的存在是Αβ沉积以及临床病理加速下降的关键环节。此外，我们的研究结果表明P-tau蛋白可以作为AD疾病相关退化的重要标志。

研究人员指出，早期干预试验应考虑脑脊液P-tau蛋白181p和脑脊液Αβ的1-42在患者体内的情况。这项研究由来自美国国立卫生研究院的资助青年学者奖、阿尔茨海默氏病影像学和阿尔茨海默氏症协会资助。（生物谷：Bioon.com）

doi:10.1001/archneurol.2011.3354
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Amyloid-β–Associated Clinical Decline Occurs Only in the Presence of Elevated P-tau

Rahul S. Desikan, MD, PhD; Linda K. McEvoy, PhD; Wesley K. Thompson, PhD; Dominic Holland, PhD; James B. Brewer, MD, PhD; Paul S. Aisen, MD; Reisa A. Sperling, MD; Anders M. Dale, PhD; for the Alzheimer's Disease Neuroimaging Initiative

Objective  To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-β (Aβ) and tau, and clinical decline over time among cognitively normal older individuals.

Design  A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments.

Setting  Research centers across the United States and Canada.

Patients:  We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination.

Main Outcome Measures  Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau181p), CSF Aβ1-42, and clinical decline as assessed using longitudinal change in global CDR, CDR–Sum of Boxes, and the Alzheimer Disease Assessment Scale–cognitive subscale.

Results  We found a significant relationship between decreased CSF Aβ1-42 and longitudinal change in global CDR, CDR–Sum of Boxes, and Alzheimer Disease Assessment Scale–cognitive subscale in individuals with elevated CSF p-tau181p. In the absence of CSF p-tau181p, the effect of CSF Aβ1-42 on longitudinal clinical decline was not significantly different from 0.

Conclusions  In cognitively normal older individuals, Aβ-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.