Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
Neurobiol Aging. 2012 Feb;33(2):234-41. doi: 10.1016/j.neurobiolaging.2010.03.001. Epub 2010 Apr 14.
Mounting evidence suggests cell cycle dysregulation is involved in the pathogenesis of Alzheimer's disease (AD) and that this failure is systemic, affecting not only neurons but also peripheral blood lymphocytes (PBLs). This study analyzed if differences in PBL proliferation activity could be used as a diagnostic biomarker for AD. CD69 and CD28 expressions on PBL T, B, and monocyte cells were measured by flow cytometry with and without mitogenic stimulation in healthy controls (HC), probable AD, and Parkinson's disease dementia (PDD) subjects. Univariate and multivariate scoring models were employed to evaluate the data relative to the clinical diagnoses. Eleven CD expression markers were significantly altered in AD subjects compared with a mixed pool of PDD and HC subjects using univariate models. Using multivariate models, seven CD expression markers were significantly altered in AD subjects compared with PDD subjects. Multivariate scoring demonstrated up to a 91% positive and 92% negative agreement with subject clinical diagnosis and had little correlation with the severity of dementia. Present findings suggest that with further development this analytical and multivariate modeling procedure could aid the current differential diagnosis of Alzheimer's disease.
越来越多的证据表明,细胞周期失调与阿尔茨海默病(AD)的发病机制有关,这种失调是全身性的,不仅影响神经元,还影响外周血淋巴细胞(PBL)。本研究分析了 PBL 增殖活性的差异是否可以作为 AD 的诊断生物标志物。通过流式细胞术,在健康对照组(HC)、可能的 AD 和帕金森病痴呆(PDD)患者中,在有丝分裂刺激和无有丝分裂刺激的情况下,测量了 PBL T、B 和单核细胞上的 CD69 和 CD28 表达。采用单变量和多变量评分模型来评估与临床诊断相关的数据。与 PDD 和 HC 混合组相比,AD 患者中有 11 个 CD 表达标志物在单变量模型中发生了显著改变。使用多变量模型,与 PDD 患者相比,AD 患者中有 7 个 CD 表达标志物发生了显著改变。多变量评分显示与患者的临床诊断具有高达 91%的阳性和 92%的阴性一致性,与痴呆的严重程度相关性较小。目前的研究结果表明,随着进一步的发展,这种分析和多变量建模过程可以辅助当前 AD 的鉴别诊断。