Blood Biomarkers for Alzheimer’s Disease: Much Promise, Cautious Progress
Abstract
Biomarkers in Alzheimer's disease (AD) have the potential to allow early and more accurate diagnosis, predict disease progression, stratify individuals and track response to candidate therapies in drug trials. The first fluid biomarkers reflecting aspects of AD neuropathology were identified in cerebrospinal fluid (CSF) in the 1990s. Three CSF biomarkers (amyloid-β 1-42, total tau and phospho-tau) have consistently been shown to have diagnostic utility and are incorporated into the new diagnostic criteria for AD. These markers have also been shown in longitudinal studies to predict conversion of mild cognitive impairment to AD. However, a key issue with the use of CSF biomarkers as a screening test is the invasiveness of lumbar puncture. Over the last 20 years there has been an active quest for blood biomarkers, which could be easily acquired and tested repeatedly throughout the disease course. One approach to identifying such markers is to attempt to measure candidates that have already been identified in CSF. Until recently, this approach has been limited by assay sensitivity, but newer platforms now allow single molecule-level detection. Another approach is identification of candidates in large multiplex panels that allow for multiple analytes to be quantified in parallel. While both approaches show promise, to date no blood-based biomarker or combination of biomarkers has sufficient predictive value to have utility in clinical practice. In this review, an overview of promising blood protein candidates is provided, and the challenges of validating and converting these into practicable tests are discussed.
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The present Elecsys assays produced among the best accuracies and are the first fully automated assays to have these greater accuracies.
“Although previous studies have found associations between CSF and PET Aβ and plasma Aβ using different immunoassays,7,12,13,14,44,45 the present Elecsys assays produced among the best accuracies and they are the first fully automated assays to have these greater accuracies.”
From Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status (2019) · cites this paper as [7]
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- Authors
- Keshavan, A., Heslegrave, A., Zetterberg, H., & Schott, J. M.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- UCL Queen Square Institute of Neurology (GB)
- Sahlgrenska University Hospital (SE)
- Corresponding author
- Schott, Jonathan M.
- Venue
- Molecular Diagnosis & Therapy
- Published
- 2016-10-13
- Volume
- 21
- Issue
- 1
- Pages
- 13-22
- ISSN
- 1177-1062 (ISSN-L)
- 1179-2000
- OpenAlex
- W2530387364
- Cited by
- 34
- References
- 59
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 4
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Diagnosis & Therapy (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Brain Research UK (UCC14181)
- National Institute for Health and Care Research (NF-SI-0508-10123)
- Medical Research Council (MR/L023784/2, MR/L023784/1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, blood biomarkers, cerebrospinal fluid biomarkers, amyloid-beta 42, total tau, phosphorylated tau, mild cognitive impairment, early diagnosis, biomarker validation, single-molecule detection, disease progression prediction, drug response monitoring
- MeSH terms
- Alzheimer Disease, Humans, Biomarkers, tau Proteins, Neurofilament Proteins, Disease Progression
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