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

Autor: Libiger O; Janssen Research and Development, San Diego, California, USA., Shaw LM; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Watson MH; Caprion Biosciences, Montreal, Quebec, Canada., Nairn AC; Yale University School of Medicine, New Haven, Connecticut, USA., Umaña KL; Foundation for the National Institutes of Health, North Bethesda, Maryland, USA., Biarnes MC; Foundation for the National Institutes of Health, North Bethesda, Maryland, USA., Canet-Avilés RM; Foundation for the National Institutes of Health, North Bethesda, Maryland, USA., Jack CR Jr; Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA., Breton YA; Caprion Biosciences, Montreal, Quebec, Canada., Cortes L; Caprion Biosciences, Montreal, Quebec, Canada., Chelsky D; Caprion Biosciences, Montreal, Quebec, Canada., Spellman DS; Merck & Co., Inc., West Point, Pennsylvania, USA., Baker SA; Janssen Research and Development, Titusville, New Jersey, USA., Raghavan N; Janssen Research and Development, Titusville, New Jersey, USA., Potter WZ; National Institute of Mental Health, Bethesda, Maryland, USA.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2021 Dec; Vol. 17 (12), pp. 1976-1987. Date of Electronic Publication: 2021 May 13.
DOI: 10.1002/alz.12353
Abstrakt: Introduction: Biomarkers that reflect pathologic processes affecting neuronal function during preclinical and early stages of Alzheimer's disease (AD) are needed to aid drug development.
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.
Discussion: CSF NPTX2 concentration is a strong prognostic biomarker candidate of accelerated cognitive decline with potential use as a therapeutic target.
(© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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