Emerging cerebrospinal fluid biomarkers in autosomal dominant Alzheimer's disease
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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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Soluble p-tau and t-tau are increased already in preclinical disease (no cognitive impairment but evidence of AD pathology).
“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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Self-citation
- 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
- Health Sciences › Medicine › Physiology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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