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Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease
Open accessAbstract
INTRODUCTION: Four less well-studied but promising "emerging" cerebrospinal fluid (CSF) biomarkers are elevated in late-onset Alzheimer disease (AD): neurogranin, synaptosomal-associated protein-25 (SNAP-25), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). METHODS: CSF neurogranin, SNAP-25, VILIP-1, and YKL-40 were measured in families carrying autosomal-dominant AD mutations. RESULTS: The four emerging CSF biomarkers were significantly elevated in the mutation carriers (n = 235) versus noncarriers (n = 145). CSF SNAP-25, VILIP-1, and YKL-40 were altered very early in the AD time course, approximately 15-19 years before estimated symptom onset. All CSF biomarkers predicted important AD-related outcomes including performance on a cognitive composite, brain amyloid burden as measured by amyloid positron emission tomography, and the estimated years from symptom onset. DISCUSSION: Early abnormalities in CSF tTau, pTau, SNAP-25, VILIP-1, and YKL-40 suggest that synaptic damage, neuronal injury, and neuroinflammation begin shortly after the commencement of brain amyloid accumulation.
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“longitudinal studies have demonstrated that soluble p-tau and t-tau are increased already in preclinical disease (e.g., no cognitive impairment but evidence of AD pathology).5,6”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [6]
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Metadata
- Authors
- Schindler, S. E., Li, Y., Todd, K. W., Herries, E. M., Henson, R. L., Gray, J. D., Wang, G., Graham, D. L., Shaw, L. M., Trojanowski, J. Q., Hassenstab, J. J., Benzinger, T. L. S., Cruchaga, C., Jucker, M., Levin, J., Chhatwal, J. P., Noble, J. M., Ringman, J. M., Graff‐Radford, N. R., Holtzman, D. M., Ladenson, J. H., Morris, J. C., Bateman, R. J., Xiong, C., Fagan, A. M., & Dominantly Inherited Alzheimer Network
- Affiliations
- Washington University in St. Louis (US)
- Biogen (United States) (US)
- University of Pennsylvania (US)
- German Center for Neurodegenerative Diseases (DE)
- Harvard University (US)
- Columbia University Irving Medical Center (US)
- University of Southern California (US)
- Mayo Clinic (US)
- Corresponding author
- Fagan, Anne M.
- ORCID
- Schindler, Suzanne E.
- Li, Yan
- Todd, Kaitlin W.
- Henson, Rachel L.
- Wang, Guoqiao
- Graham, Danielle L.
- Shaw, Leslie M.
- Trojanowski, John Q.
- Hassenstab, Jason J.
- Benzinger, Tammie L.S.
- Cruchaga, Carlos
- Jucker, Mathias
- Levin, Johannes
- Chhatwal, Jasmeer P.
- Noble, James M.
- Ringman, John M.
- Graff‐Radford, Neill R.
- Holtzman, David M.
- Morris, John C.
- Bateman, Randall J.
- Xiong, Chengjie
- Fagan, Anne M.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2019-03-04
- Volume
- 15
- Issue
- 5
- Pages
- 655-665
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6511459
- OpenAlex
- W2920691528
- Cited by
- 101
- References
- 54
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 10 · 2022: 20 · 2021: 18 · 2020: 19 · 2019: 6
- FWCI
- 10.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DZNE Pub (submittedVersion)
- Funders
- Avid Radiopharmaceuticals
- AbbVie
- Biogen
- Fujirebio US
- CS Fund (Ng, SNAP‐25, YKL‐40, VILIP‐1)
- National Institute on Aging
- Japan Agency for Medical Research and Development
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- cerebrospinal fluid biomarkers, autosomal dominant Alzheimer's disease
- MeSH terms
- Chitinase-3-Like Protein 1, Aged, Alzheimer Disease, Female, Humans, Inflammation, Male, Middle Aged, Mutation, Biomarkers, Amyloid beta-Peptides, Disease Progression, Positron-Emission Tomography, Synaptosomal-Associated Protein 25, Neurogranin, Neurocalcin
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