Large‐scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer's disease
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We surveyed a total of 570 cerebrospinal fluid (CSF) samples from a variety of diseases, including Alzheimer's disease (AD; n = 236), non‐AD‐demented and nondemented diseases (n = 239), and normal controls (n = 95) to quantitate levels of tau protein phosphorylated at serine 199 (CSF/phospho‐tau 199) by a recently established sandwich ELISA. The CSF/phospho‐tau 199 levels in the AD group were significantly elevated compared to those in all the other non‐AD groups. Receiver operating characteristics curves showed that the diagnostic sensitivity and specificity for the AD group versus all the other non‐AD groups using the CSF/phospho‐tau 199 were 85.2% and 85.0%, respectively. Furthermore, there was a significant positive correlation between CSF/phospho‐tau 199 and CSF/total‐tau levels in the AD group. Elevated CSF/phospho‐tau 199 in the AD group was noted irrespective of age, gender, dementia severity, and number of apolipoprotein E4 alleles. Thus, we suggest that CSF/phospho‐tau 199 may be a novel and logical biomarker in supporting antemortem diagnosis of AD.
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Elevated CSF concentrations of total tau and tau phosphorylated at amino acids 181 and 217 are surprisingly AD-specific; tau-associated FTD subtypes do not have elevated CSF t-tau and p-tau concentrations, at least not to the levels present in AD.
“It has been shown that elevated CSF concentrations of total tau (t‐tau) and tau phosphorylated at amino acids 181 and, more recently, 217 (p‐tau181 and p‐tau217, respectively) are surprisingly AD‐specific; tau‐associated FTD subtypes do not have elevated CSF t‐tau and p‐tau concentrations, 57 , 58 , 59 , 60 at least not to the levels present in AD.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [59]
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- Authors
- Itoh, N., Arai, H., Urakami, K., Ishiguro, K., Ohno, H., Hampel, H., Buerger, K., Wiltfang, J., Otto, M., Kretzschmar, H., Moeller, H., Imagawa, M., Kohno, H., Nakashima, K., Kuzuhara, S., Sasaki, H., & Imahori, K.
- Affiliations
- Mie University (JP)
- Tohoku University (JP)
- Tottori University (JP)
- Mitsubishi Group (Japan) (JP)
- Ludwig-Maximilians-Universität München (DE)
- University of Göttingen (DE)
- Institut für Neuropathologie (DE)
- Corresponding author
- Arai, Hiroyuki
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2001-07-30
- Volume
- 50
- Issue
- 2
- Pages
- 150-156
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2145396074
- Cited by
- 256
- References
- 32
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 23 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 12 · 2012: 10
- FWCI
- 10.52
- Type
- journal article
- Language
- en
- Open access
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- GRO (submittedVersion, cc-by)
- 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, cerebrospinal fluid, tau protein, biomarkers, antemortem diagnosis, sandwich ELISA, sensitivity and specificity, APOE ε4, dementia severity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Enzyme-Linked Immunosorbent Assay, Female, Genotype, Humans, Male, Middle Aged, Phosphorylation, ROC Curve, Serine, Sex Factors, Reproducibility of Results, Biomarkers, tau Proteins, Apolipoprotein E4
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