Cited by 241Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum

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Milà‐Alomà, Marta, Salvadó, Gemma, Gispert, Juan Domingo, Vilor‐Tejedor, Natalia, Grau‐Rivera, Oriol, Sala‐Vila, Aleix, Sánchez‐Benavides, Gonzalo, Arenaza‐Urquijo, Eider M. +11 more·2020·Alzheimer's & Dementia

Abstract

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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  • CSF sample collection and processing followed standard procedures.

    “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]

    The Methods section (ALFA participants and study design; page unavailable) says CSF samples were obtained by lumbar puncture following standard procedures, supporting the collection part. The cited text does not say that sample processing followed standard procedures; the CSF biomarker measurements section describes assays rather than sample processing. (LLM, conf=0.85)

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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
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2020-06-23
Volume
16
Issue
10
Pages
1358-1371
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
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
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
  • 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
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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