Janssen Research and Development, San Diego, California, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alzheimers Dement. 2021 Dec;17(12):1976-1987. doi: 10.1002/alz.12353. Epub 2021 May 13.
Biomarkers that reflect pathologic processes affecting neuronal function during preclinical and early stages of Alzheimer's disease (AD) are needed to aid drug development.
A targeted, stable isotope, quantitative mass spectrometry-based investigation of longitudinal changes in concentrations of previously identified candidate biomarkers was performed in cerebrospinal fluid (CSF) of Alzheimer's Disease Neuroimaging Initiative participants who were classified as cognitively normal (CN; n = 76) or with mild cognitive impairment (MCI; n = 111) at baseline.
Of the candidate biomarkers, the CSF concentration of neuronal pentraxin 2 (NPTX2), a protein involved in synaptic function, exhibited rates of change that were significantly different between three comparison groups (i.e., CN vs. MCI participants; AD pathology positive vs. negative defined by phosphorylated tau181/amyloid beta1-42 ratio; and clinical progressors vs. non-progressors). The rate of change of NPTX2 also significantly correlated with declining cognition.
CSF NPTX2 concentration is a strong prognostic biomarker candidate of accelerated cognitive decline with potential use as a therapeutic target.
需要生物标志物来反映阿尔茨海默病（AD）临床前和早期阶段影响神经元功能的病理过程，以帮助药物开发。
对阿尔茨海默病神经影像学倡议参与者的脑脊液（CSF）中先前确定的候选生物标志物浓度的纵向变化进行了靶向、稳定同位素、定量质谱分析，这些参与者在基线时被分类为认知正常（CN；n=76）或轻度认知障碍（MCI；n=111）。
在候选生物标志物中，神经元五聚素 2（NPTX2）的 CSF 浓度发生变化，这是一种参与突触功能的蛋白质，在三个比较组之间（即 CN 与 MCI 参与者；AD 病理学阳性与阴性由磷酸化 tau181/淀粉样β1-42 比值定义；以及临床进展者与非进展者）的变化率明显不同。NPTX2 的变化率也与认知能力下降显著相关。
CSF NPTX2 浓度是加速认知衰退的有力预后生物标志物候选物，具有作为治疗靶点的潜力。
