Journal
ALZHEIMERS & DEMENTIA
Volume 17, Issue 12, Pages 1976-1987Publisher
WILEY
DOI: 10.1002/alz.12353
Keywords
Alzheimer' s disease; dementia; longitudinal cerebrospinal fluid; mild cognitive impairment; neuropathology; prognostic biomarker; stable isotope‐ based quantitative mass spectrometry
Categories
Funding
- Genentech
- H. Lundbeck A/S
- Janssen Research & Development, LLC
- Merck Co., Inc.
- Takeda Pharmaceutical Company Limited
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U19 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC
- Johnson & Johnson Pharmaceutical Research & Development LLC
- Lumosity
- Lundbeck
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Transition Therapeutics
- Canadian Institutes of Health Research
- Bristol-Myers Squibb Company
- CereSpir, Inc.
- Cogstate
- Eisai Inc.
- Foundation for the National Institutes of Health
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This study utilized stable isotope, quantitative mass spectrometry to investigate changes in CSF NPTX2 concentration in different comparison groups. The results suggest that NPTX2 could be a strong prognostic biomarker candidate for accelerated cognitive decline.
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.
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