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Cited by 162Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

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Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer’s disease

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Sutphen, Courtney L., McCue, Lena, Herries, Elizabeth M., Xiong, Chengjie, Ladenson, Jack H., Holtzman, David M., Fagan, Anne M., On behalf of ADNI·2018·Alzheimer's & Dementia
DOI 10.1016/j.jalz.2018.01.012PMC PMC6110083
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Abstract

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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Crossref · 10.1016/j.jalz.2018.01.012

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Fig. 1. Baseline concentrations and estimated within-person 5-year change in CSF biomarkers. Baseline biomarker concentrations (top, gray panel) and estimated group slopes (bottom, white panel) for Aβ42 (A), tTau (B), pTau (C), VILIP-1 (D), SNAP-25 (E), Ng (F), and YKL-40 (G). Baseline is shown for each individual, estimated group slopes of average annual change in five bins defined by diagnostic group and amyloid status are extrapolated to show 5 years of change. A Different from CN− group, B Different from CN + group, C Different from MCI + group, D Different from AD + group, E Different from MCI− group, * Different from 0. Abbreviations: Aβ; β amyloid; tTau, total tau; pTau, phospho-tau; VILIP-1, visinin-like protein 1; SNAP-25, synaptosomal-associated protein 25; Ng, neurogranin; YKL-40, chitinase-3 like-1.
Fig. 1. Baseline concentrations and estimated within-person 5-year change in CSF biomarkers. Baseline biomarker concentrations (top, gray panel) and estimated group slopes (bottom, white panel) for Aβ42 (A), tTau (B), pTau (C), VILIP-1 (D), SNAP-25 (E), Ng (F), and YKL-40 (G). Baseline is shown for each individual, estimated group slopes of average annual change in five bins defined by diagnostic group and amyloid status are extrapolated to show 5 years of change. A Different from CN− group, B Different from CN + group, C Different from MCI + group, D Different from AD + group, E Different from MCI− group, * Different from 0. Abbreviations: Aβ; β amyloid; tTau, total tau; pTau, phospho-tau; VILIP-1, visinin-like protein 1; SNAP-25, synaptosomal-associated protein 25; Ng, neurogranin; YKL-40, chitinase-3 like-1.CC BY-NC-ND · PubMed Central

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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.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2018-03-24
Volume
14
Issue
7
Pages
869-879
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1016/j.jalz.2018.01.012
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
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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