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Cited by 64Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsClinical Laboratory Practices and Quality Control

Alzheimer disease biomarkers: moving from CSF to plasma for reliable detection of amyloid and tau pathology

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Kang, Ju Hee, Korecka, Magdalena, Lee, Edward B, Cousins, Katheryn A Q, Tropea, Thomas F, Chen-Plotkin, Alice A, Irwin, David J, Wolk, David +3 more·2023·Clinical Chemistry
DOI 10.1093/clinchem/hvad139PMC PMC10895336
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Abstract

Background: Development of validated biomarkers to detect early Alzheimer disease (AD) neuropathology is needed for therapeutic AD trials. Abnormal concentrations of “core” AD biomarkers, cerebrospinal fluid (CSF) amyloid beta1–42, total tau, and phosphorylated tau correlate well with neuroimaging biomarkers and autopsy findings. Nevertheless, given the limitations of established CSF and neuroimaging biomarkers, accelerated development of blood-based AD biomarkers is underway. Content: Here we describe the clinical significance of CSF and plasma AD biomarkers to detect disease pathology throughout the Alzheimer continuum and correlate with imaging biomarkers. Use of the AT(N) classification by CSF and imaging biomarkers provides a more objective biologically based diagnosis of AD than clinical diagnosis alone. Significant progress in measuring CSF AD biomarkers using extensively validated highly automated assay systems has facilitated their transition from research use only to approved in vitro diagnostics tests for clinical use. We summarize development of plasma AD biomarkers as screening tools for enrollment and monitoring participants in therapeutic trials and ultimately in clinical care. Finally, we discuss the challenges for AD biomarkers use in clinical trials and precision medicine, emphasizing the possible ethnocultural differences in the levels of AD biomarkers. Summary: CSF AD biomarker measurements using fully automated analytical platforms is possible. Building on this experience, validated blood-based biomarker tests are being implemented on highly automated immunoassay and mass spectrometry platforms. The progress made developing analytically and clinically validated plasma AD biomarkers within the AT(N) classification scheme can accelerate use of AD biomarkers in therapeutic trials and routine clinical practice.

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  • Aß and tau proteoforms are the most reliable fluid biomarkers for AD in both CSF and plasma.

    “which are the most reliable fluid biomarkers for AD in both CSF and plasma. 47”

    From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [47]

    The Introduction identifies Aβ42 and tau measures as core, clinically reliable CSF biomarkers. The sections on plasma Aβ and p-tau report diagnostic utility, but the Introduction says plasma biomarkers require further rigorous validation. The paper therefore supports their importance in both fluids, not the unqualified claim that they are the most reliable in both. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Kang, J. H., Korecka, M., Lee, E. B., Cousins, K. A. Q., Tropea, T. F., Chen-Plotkin, A. A., Irwin, D. J., Wolk, D., Brylska, M., Wan, Y., & Shaw, L. M.
Affiliations
  • Inha University (KR)
  • University of Pennsylvania (US)
  • Department of Neurology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , United States
Corresponding author
  • Kang, Ju Hee
  • Shaw, Leslie M
ORCID
Venue
Clinical Chemistry
Publisher
Oxford University Press (OUP)
Published
2023-09-19
Volume
69
Issue
11
Pages
1247-1259
ISSN
  • 0009-9147 (ISSN-L)
  • 1530-8561
DOI
10.1093/clinchem/hvad139
PMC
PMC10895336
OpenAlex
W4386845260
Cited by
64
References
21
Citations by year
2026: 37 · 2025: 22 · 2024: 5
FWCI
12.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, other-oa)
Funders
National Research Foundation funded (NRF-2021RIA5A2031612)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
Alzheimer's disease, Alzheimer's disease biomarkers, plasma biomarkers, cerebrospinal fluid biomarkers, amyloid-beta 42, total tau, phosphorylated tau, amyloid pathology, tau pathology, blood-based biomarkers, precision medicine, in vitro diagnostics, automated immunoassay, mass spectrometry
MeSH terms
Alzheimer Disease, Humans, Immunoassay, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins

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