Comparison of CSF phosphorylated tau 181 and 217 for cognitive decline
Open accessAbstract
Introduction: The prognostic utility of cerebrospinal fluid (CSF) phosphorylated tau 217 (p‐tau217) and p‐tau181 is not understood. Methods: Analyses included 753 Mayo Clinic Study on Aging participants (median age = 71.6; 57% male). CSF amyloid beta (Aβ)42 and p‐tau181 were measured with Elecsys immunoassays. CSF p‐tau181 and p‐tau217 were also measured with Meso Scale Discovery (MSD). We used Cox proportional hazards models for risk of mild cognitive impairment (MCI) and linear mixed models for risk of global and domain‐specific cognitive decline and cortical thickness. Analyses were stratified by elevated brain amyloid based on CSF Aβ42 or amyloid positron emission tomography for those with imaging. Results: CSF p‐tau217 was superior to p‐tau181 for the diagnosis of Alzheimer's disease (AD) pathology. CSF MSD p‐tau181 and p‐tau217 were associated with risk of MCI among amyloid‐positive individuals. Differences between CSF p‐tau measures predicting cortical thickness were subtle. Discussion: There are subtle differences for CSF p‐tau217 and p‐tau181 as prognostic AD markers.
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Among p-tau variants, p-tau217 has demonstrated the highest accuracy in detecting AD pathology and predicting future cognitive decline.
“Among different p-tau variants, tau phosphorylated at threonine 217 (p-tau217) has demonstrated the highest accuracy in detecting AD pathology and predicting future cognitive decline23,27,29–31.”
From Highly accurate blood test for Alzheimer's disease is similar or superior to clinical cerebrospinal fluid tests (2024) · cites this paper as [31]
The Discussion reports better diagnostic performance for CSF p-tau217 than p-tau181, and the Results report a higher AUC for p-tau217 in several comparisons of amyloid status (section 3.2). But the study compares p-tau217 only with p-tau181, not all p-tau variants; for cognitive decline, the Discussion says differences between the measures were subtle. It therefore does not establish the claimed highest accuracy for predicting future cognitive decline. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCSF p-tau217 might better discriminate AD from other neurodegenerative diseases than CSF p-tau181.
“Recent reports have suggested that CSF p-tau217 might better discriminate AD from other neurodegenerative diseases24,27, 28, 29, 30 than CSF p-tau181.”
From Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease (2022) · cites this paper as [29]
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References 34 · Cited by 55
Research works printed but not linked: 1
- [34]34. Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, et al. CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 2016;3:154-165. [PubMed: 27042676]
- Authors
- Mielke, M. M., Aakre, J. A., Algeciras‐Schimnich, A., Proctor, N. K., Machulda, M. M., Eichenlaub, U., Knopman, D. S., Vemuri, P., Graff‐Radford, J., Jack, C. R., Petersen, R. C., & Dage, J. L.
- Affiliations
- Mayo Clinic (US)
- Eli Lilly (United States) (US)
- Roche Diagnostics GmbH Penzberg Germany
- Corresponding author
- Mielke, Michelle M.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2021-07-26
- Volume
- 18
- Issue
- 4
- Pages
- 602-611
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC8789950
- OpenAlex
- W3184936796
- Cited by
- 55
- References
- 34
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 16 · 2023: 10 · 2022: 11 · 2021: 1
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Aging (U01 AG006786, P30 AG062677, R01 AG011378, R01 AG041851)
- 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
- phosphorylated tau 181, phosphorylated tau217
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Male, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Cognitive Dysfunction
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