Fluid Biomarkers in Alzheimer Disease
Open accessAbstract
Research progress has provided detailed understanding of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new drug candidates with putative disease-modifying effects, which are now being tested in clinical trials. The promise of effective therapy has created a great need for biomarkers able to detect AD in the predementia phase, because drugs will probably be effective only if neurodegeneration is not too advanced. In this chapter, cerebrospinal fluid (CSF) and plasma biomarkers are reviewed. The core CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of β-amyloid (Aβ42) reflect AD pathology, and have high diagnostic accuracy to diagnose AD with dementia and prodromal AD in mild cognitive impairment cases. The rationale for the use of CSF biomarkers to identify and monitor the mechanism of action of new drug candidates is also outlined in this chapter.
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Aβ42 levels decrease in the CSF as Aβ starts to accumulate, before fibrillar plaques can be detected with PET.
“Previous cross-sectional studies indicate that Aβ42 levels decrease in the CSF as Aβ starts to accumulate, before fibrillar plaques can be detected with PET7–11.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [8]
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“Further, although no study has examined the added diagnostic value of PIB-PET and CSF biomarkers, there is a strict negative correlation between the degree of PIB binding as seen in PET images and the CSF level of Ab42 (Fagan et al. 2006, 2009b; Forsberg et al. 2008; Grimmer et al. 2009).”
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Biochemical markers in persons with preclinical familial Alzheimer disease
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Self-citationThe precursor of Alzheimer??s disease amyloid A4 protein resembles a cell-surface receptor
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High Levels of Circulating Aβ42 Are Sequestered by Plasma Proteins in Alzheimer's Disease
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Cytoskeleton proteins in CSF distinguish frontotemporal dementia from AD
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Self-citationLewy Body Pathology in Alzheimer's Disease
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A novel pathway for amyloid precursor protein processing
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CSF biomarkers in the evaluation of idiopathic normal pressure hydrocephalus
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Self-citationRelationship of Cerebrospinal Fluid Markers to11C-PiB and18F-FDDNP Binding
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Self-citationEffect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease
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Self-citationCerebrospinal fluid total tau as a marker of Alzheimer's disease intensity
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Self-citationIdentification of Novel Brain Biomarkers
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CSF biomarkers for Alzheimer’s disease: use in early diagnosis and evaluation of drug treatment
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Intra-Individual Stability of CSF Biomarkers for Alzheimer's Disease over Two Years
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An Alzheimer's disease-specific β-amyloid fragment signature in cerebrospinal fluid
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Self-citationAmyloid β 38, 40, and 42 species in cerebrospinal fluid: More of the same?
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CSF and MRI markers independently contribute to the diagnosis of Alzheimer's disease
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Brain Atrophy in Healthy Aging Is Related to CSF Levels of Aβ1-42
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Self-citationIncreased cerebrospinal fluid levels of transforming growth factor-β1 in Alzheimer’s disease
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Increased β‐Secretase activity in cerebrospinal fluid of Alzheimer's disease subjects
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Familial Alzheimer disease: Decreases in CSF Aβ 42 levels precede cognitive decline
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Detection of amyloid in Alzheimer’s disease with positron emission tomography using [11C]AZD2184
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Markers of Alzheimer's disease in a population attending a memory clinic
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Alzheimer’s disease risk variants show association with cerebrospinal fluid amyloid beta
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Self-citationCharacterization of Tau in Cerebrospinal Fluid Using Mass Spectrometry
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Usefulness of computed tomography linear measurements in diagnosing alzheimer's disease
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Diagnostic accuracy of Alzheimer’s disease: A clinicopathological study
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F2-Isoprostanes as Biomarkers of Late-onset Alzheimer’s Disease
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Self-citationBiomarkers for Alzheimer's disease
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How can we recognize “disease modification” effects?
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Self-citationMetabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model
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Self-citationPain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine
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- Authors
- Blennow, K., Zetterberg, H., & Fagan, A. M.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Washington University in St. Louis (US)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2012-04-17
- Volume
- 2
- Issue
- 9
- Pages
- a006221-a006221
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3426814
- OpenAlex
- W2150585091
- Cited by
- 208
- References
- 175
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 13 · 2023: 14 · 2022: 14 · 2021: 10 · 2020: 9 · 2019: 21 · 2018: 14 · 2017: 14 · 2016: 14 · 2015: 24 · 2014: 21 · 2013: 24 · 2012: 6
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- 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, fluid biomarkers, cerebrospinal fluid biomarkers, plasma biomarkers, total tau, phosphorylated tau, amyloid-beta 42, prodromal Alzheimer's disease, mild cognitive impairment, dementia diagnosis
- MeSH terms
- Alzheimer Disease, Cerebrospinal Fluid Proteins, Humans, Isomerism, Isotope Labeling, Neuritis, Phosphorylation, Biomarkers, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, tau Proteins, Neurofilament Proteins, Oxidative Stress, Amyloid Precursor Protein Secretases, Biomarkers, Pharmacological
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