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Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer’s disease
Open accessAbstract
INTRODUCTION: Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design. METHODS: Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid status. RESULTS: Levels of injury markers were highly positively correlated. Despite elevated baseline levels as a function of clinical status and amyloid-positivity, within-person decreases in these measures were observed in the early symptomatic, amyloid-positive Alzheimer's disease group. DISCUSSION: Knowledge of within-person biomarker change will impact interpretation of biomarker outcomes in clinical trials that are dependent on disease stage.
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“At the time of tau positivity, during neurodegeneration and cognitive abnormalities phases, CSF p-tau epitopes have largely reached a plateau.66”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [66]
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“Neurogranin (a key regulator of the calcium-binding protein calmodulin), synaptogamin (a calcium sensor protein), and SNAP-25 (a component of the SNARE [soluble N-ethylmaleimide sensitive factor attachment protein receptor] complex) are the strongest candidates for in vivo tracking synaptic homeostasis (131–133).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [133]
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Metadata
- Authors
- Sutphen, C. L., McCue, L., Herries, E. M., Xiong, C., Ladenson, J. H., Holtzman, D. M., Fagan, A. M., & On behalf of, A. D. N. I.
- Affiliations
- Washington University in St. Louis (US)
- Alzheimer’s Disease Neuroimaging Initiative (US)
- Corresponding author
- Fagan, Anne M.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-03-24
- Volume
- 14
- Issue
- 7
- Pages
- 869-879
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6110083
- OpenAlex
- W2791314414
- Cited by
- 162
- References
- 42
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 19 · 2023: 10 · 2022: 22 · 2021: 32 · 2020: 35 · 2019: 18 · 2018: 3
- FWCI
- 17.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (P50AG005681, P01AG003991, P01AG026276, U01 AG024904)
- U.S. Department of Defense (W81XWH‐12‐2‐0012)
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Northern California Institute for Research and Education
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid biomarkers
- MeSH terms
- Aged, Alzheimer Disease, Cognition, Female, Humans, Longitudinal Studies, Male, Biomarkers, Amyloid beta-Peptides, tau Proteins, Age of Onset, Synaptosomal-Associated Protein 25, Neurocalcin, Cognitive Dysfunction
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