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Alzheimers Dement ; 17(12): 1976-1987, 2021 12.
Article in English | MEDLINE | ID: mdl-33984181

ABSTRACT

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.


Subject(s)
Alzheimer Disease , Biomarkers/cerebrospinal fluid , C-Reactive Protein/cerebrospinal fluid , Cognitive Dysfunction , Nerve Tissue Proteins/cerebrospinal fluid , Proteomics , Aged , Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/pathology , Amyloid beta-Peptides/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Cognitive Dysfunction/pathology , Humans , Longitudinal Studies , Mass Spectrometry , Phosphorylation , tau Proteins/cerebrospinal fluid
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