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Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum
Open accessAbstract
Introduction: The biological pathways involved in the preclinical stage of the Alzheimer's continuum are not well understood. Methods: We used NeuroToolKit and Elecsys ® immunoassays to measure cerebrospinal fluid (CSF) amyloid‐β (Aβ)42, Aβ40, phosphorylated tau (p‐tau), total tau (t‐tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100, and α‐synuclein in cognitively unimpaired participants of the ALFA+ study, many within the Alzheimer's continuum . Results: CSF t‐tau, p‐tau, and neurogranin increase throughout aging only in Aβ‐positive individuals, whereas NfL and glial biomarkers increase with aging regardless of Aβ status. We modelled biomarker changes as a function of CSF Aβ42/40, p‐tau and p‐tau/Aβ42 as proxies of disease progression. The first change observed in the Alzheimer's continuum was a decrease in the CSF Aβ42/40 ratio. This is followed by a steep increase in CSF p‐tau; t‐tau; neurogranin; and, to a lesser extent, in NfL and glial biomarkers. Discussion: Multiple biological pathways are altered and could be targeted very early in the Alzheimer's continuum .
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“The CSF sample collection and processing followed standard procedures25 and have been described previously15.”
From Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease (2022) · cites this paper as [15]
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Cites
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“The Elecsys β-Amyloid (1-42) CSF immunoassay in use is not a commercially available IVD assay.”
MethodRobust Locally Weighted Regression and Smoothing Scatterplots
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“The Elecsys β-Amyloid (1-42) CSF immunoassay in use is not a commercially available IVD assay.”
MethodNIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
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“The Elecsys β-Amyloid (1-42) CSF immunoassay in use is not a commercially available IVD assay.”
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Metadata
- Authors
- Milà‐Alomà, M., Salvadó, G., Gispert, J. D., Vilor‐Tejedor, N., Grau‐Rivera, O., Sala‐Vila, A., Sánchez‐Benavides, G., Arenaza‐Urquijo, E. M., Crous‐Bou, M., González‐de‐Echávarri, J. M., Minguillon, C., Fauria, K., Simon, M., Kollmorgen, G., Zetterberg, H., Blennow, K., Suárez‐Calvet, M., Molinuevo, J. L., & study, F. T. A.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Pasqual Maragall Foundation (ES)
- Barcelonaβeta Brain Research Center (BBRC) Pasqual Maragall Foundation Barcelona Spain
- Harvard University (US)
- F. Hoffmann-La Roche AG (CH)
- Roche Diagnostics GmbH Penzberg Germany
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Suárez‐Calvet, Marc
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2020-06-23
- Volume
- 16
- Issue
- 10
- Pages
- 1358-1371
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC7586814
- OpenAlex
- W3037038790
- Cited by
- 241
- References
- 51
- Citations by year
- 2026: 30 · 2025: 45 · 2024: 53 · 2023: 34 · 2022: 41 · 2021: 33 · 2020: 5
- FWCI
- 17.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by-nc-nd)
- EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- “la Caixa” Foundation (ID 100010434)
- 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
- preclinical Alzheimer's disease
- MeSH terms
- Aged, Alzheimer Disease, Brain, Female, Humans, Longitudinal Studies, Male, Middle Aged, Nerve Degeneration, Neuroglia, Synapses, Biomarkers, Amyloid beta-Peptides, tau Proteins, Prodromal Symptoms
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