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Cerebrospinal Fluid Tau and β-Amyloid: How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?
Abstract
Background Tau and beta-amyloid (Abeta) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific pathology, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. Objectives To correlate antemortem cerebrospinal fluid (CSF) tau and Abeta levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Abeta. Design Prospective study. Setting Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. Main outcome measures Correlation of CSF tau and Abeta with final diagnosis. Results Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Abeta42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). Conclusions Elev…
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“low concentrations of Aβ42 in the cerebrospinal fluid (CSF) reflect the presence of cerebral Aβ deposition, likely as a result of Aβ42 being sequestered into amyloid plaques, changing the equilibrium between the brain and CSF pools of Aβ (20-22).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [21]
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Metadata
- Authors
- Clark, C. M., Xie, S., Chittams, J., Ewbank, D., Peskind, E., Galasko, D., Morris, J. C., McKeel, D. W., Farlow, M., Weitlauf, S. L., Quinn, J., Kaye, J., Knopman, D., Arai, H., Doody, R. S., DeCarli, C., Leight, S., Lee, V. M.-Y., & Trojanowski, J. Q.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Clark, Christopher M.
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2003-12-01
- Volume
- 60
- Issue
- 12
- Pages
- 1696
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2156024136
- Cited by
- 357
- References
- 43
- Citations by year
- 2025: 9 · 2024: 9 · 2023: 14 · 2022: 5 · 2021: 7 · 2020: 12 · 2019: 20 · 2018: 8 · 2017: 10 · 2016: 15 · 2015: 16 · 2014: 21 · 2013: 14 · 2012: 25
- FWCI
- 8.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50ag008664-09, 5r01ag008419-15)
- National Institute on Aging (AG 10133, P30AG010133, AG08419, AG 08017, AG03991, AG05131, AG 05136, P50AG005131, AG-08664, P30AG010124, AG 05681, P30AG008017, AG-10124, P50AG005681, P01AG003991, P50AG005136)
- 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
- cerebrospinal fluid tau, amyloid-beta, Alzheimer's disease, dementia biomarkers, diagnostic biomarkers, frontal lobe dementia, dementia with Lewy bodies, prion disease, mixed dementia, antemortem diagnosis, amyloid-beta 42
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Humans, Middle Aged, Prospective Studies, ROC Curve, Cohort Studies, Biomarkers, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Area Under Curve, Lewy Body Disease
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