Longitudinal CSF proteomics identifies NPTX2 as a prognostic biomarker of Alzheimer's disease

纵向 CSF 蛋白质组学鉴定出 NPTX2 是阿尔茨海默病的预后生物标志物

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作者:Ondrej Libiger, Leslie M Shaw, Mark H Watson, Angus C Nairn, Kelly L Umaña, Michael C Biarnes, Rosa M Canet-Avilés, Clifford R Jack Jr, Yannick-André Breton, Laetitia Cortes, Daniel Chelsky, Daniel S Spellman, Susan A Baker, Nandini Raghavan, William Z Potter; Alzheimer's Disease Neuroimaging Initia

Discussion

CSF NPTX2 concentration is a strong prognostic biomarker candidate of accelerated cognitive decline with potential use as a therapeutic target.

Methods

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.

Results

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.

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