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Biomarkers for the Early Detection and Progression of Alzheimer's Disease
Open accessAbstract
The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible. In this regard, positive amyloid or tau tracer retention on positron emission tomography imaging, low CSF concentrations of the amyloid-β 1-42 peptide, high CSF concentrations in total tau and phospho-tau, mesial temporal lobe atrophy on magnetic resonance imaging, and temporoparietal/precuneus hypometabolism or hypoperfusion on 18F-fluorodeoxyglucose positron emission tomography have all emerged as biomarkers for the progression to AD. However, the ultimate AD biomarker panel will likely involve the inclusion of novel CSF and blood biomarkers more precisely associated with confirmed pathophysiologic mechanisms to improve its reliability for detecting preclinical AD. This review highlights advancements in biological fluid and imaging biomarkers that are moving the field towards achieving the goal of a preclinical detection of AD.
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“Previous studies revealed that Aβ began to accumulate up to 15–20 years prior to clinical symptoms of Alzheimer’s disease42,43.”
From Integrated algorithm combining plasma biomarkers and cognitive assessments accurately predicts brain β-amyloid pathology (2023) · cites this paper as [43]
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Metadata
- Authors
- Counts, S. E., Ikonomovic, M. D., Mercado, N., Vega, I. E., & Mufson, E. J.
- Affiliations
- Trinity Health Grand Rapids (US)
- Michigan State University (US)
- Barrow Neurological Institute (US)
- Corresponding author
- Mufson, Elliott J.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 14
- Issue
- 1
- Pages
- 35-53
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC5233625
- OpenAlex
- W2529983878
- Cited by
- 224
- References
- 296
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 35 · 2023: 27 · 2022: 24 · 2021: 33 · 2020: 22 · 2019: 18 · 2018: 11 · 2017: 3
- FWCI
- 1.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG043375, AG026032)
- National Intitute on Aging (AG042146)
- BNI Barrow and Beyond
- Saint Mary’s Foundation
- Miles for Memories of Battle Creek
- National Insitute of Aging (PO1AG025204)
- 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, biomarkers, early detection, preclinical Alzheimer's disease, disease progression, cerebrospinal fluid biomarkers, amyloid-beta 42, total tau, phosphorylated tau, amyloid PET, tau PET, FDG-PET, blood biomarkers
- MeSH terms
- Alzheimer Disease, Autoantibodies, Humans, Sensitivity and Specificity, Biomarkers, Amyloid beta-Peptides, Disease Progression, Inflammation Mediators, Early Diagnosis, Positron-Emission Tomography
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