Soluble P‐tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau
Open accessAbstract
Alzheimer's disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer's disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P-tau217, but P-tau217 was not elevated in patients with non-Alzheimer's disease tauopathies (N = 9). Several findings were replicated in a cohort with PET imaging ("BioFINDER-2", N = 426), where β-amyloid and tau PET were independently associated with P-tau217. P-tau217 concentrations correlated with β-amyloid PET (but not tau PET) in early disease stages and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 concentration is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.
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Certain p-tau species, but not all, are also associated with neurofibrillary tangle pathology, the secondary AD pathological hallmark.
“Yet certain p-tau species, but not all, are also associated with neurofibrillary tangle pathology, the secondary AD pathological hallmark.15,16,17”
From Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology (2024) · cites this paper as [15]
The Results and Discussion report that plasma P-tau217 is associated with tau tangles in cases with Aβ pathology, supporting the claim for one p-tau species. The paper does not establish that other p-tau species lack this association; its negative findings concern P-tau217 in particular pathological settings, not a comparison across species. The supplied passages have section labels but no page numbers. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPlasma tau has emerged as a marker of neuronal distress and appears in several neurodegenerative diseases, including preclinical AD.
“Like NfL (neurofilament light chain), plasma tau has emerged as a marker of neuronal distress. It appears in several different neurodegenerative diseases, including importantly even preclinical AD patients (76–85).”
From All the Tau We Cannot See (2023) · cites this paper as [82]
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- Authors
- Mattsson‐Carlgren, N., Janelidze, S., Bateman, R. J., Smith, R., Stomrud, E., Serrano, G. E., Reiman, E. M., Palmqvist, S., Dage, J. L., Beach, T. G., & Hansson, O.
- Affiliations
- Lund University (SE)
- Washington University in St. Louis (US)
- Banner Alzheimer’s Institute (US)
- Eli Lilly (United States) (US)
- Banner Sun Health Research Institute (US)
- Corresponding author
- Hansson, Oskar
- ORCID
- Venue
- EMBO Molecular Medicine
- Published
- 2021-05-05
- Volume
- 13
- Issue
- 6
- Pages
- e14022-e14022
- ISSN
- 1757-4676 (ISSN-L)
- 1757-4684
- PMC
- PMC8185545
- OpenAlex
- W3128184462
- Cited by
- 261
- References
- 21
- Citations by year
- 2026: 64 · 2025: 65 · 2024: 37 · 2023: 52 · 2022: 36 · 2021: 7
- FWCI
- 20.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- EMBO Molecular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by)
- Funders
- The Swedish Research council (2016‐00906)
- Kunt and Alice Wallenberg Foundation (2017‐0383)
- Medical Faculty, Lund University and Region Skåne (NMC 2019‐2022)
- The Marianne and Marcus Wallenberg Foundation (2015.0125)
- The Strategic Research Area MultiPark, Lund University
- The Swedish Alzheimer Foundation (AF‐939932)
- The Swedish Brain Foundation (FO2019‐0326, FO2020‐0275)
- The Parkinson foundation of Sweden (1280/20)
- The Skåne University Hospital Foundation (2020‐O000028)
- Regionalt Forskningsstöd (2020‐0314)
- The Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (2020 NMC)
- The Bundy Academy (Stora Priset 2020 NMC)
- Swedish Federal Government under the ALF agreement (2018‐Projekt0279, 2018‐Projekt0054)
- National Institute of Neurological Disorders and Stroke (U24 NS072026)
- National Institute on Aging (P30 AG19610)
- The Arizona Department of Health Services
- The Arizona Biomedical Research Commission (4001 0011 05‐901 1001)
- The Michael J. Fox Foundation for Parkinson's Research
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid plaques, tau tangles, plasma biomarkers, amyloid PET, tau PET, disease stage, postmortem neuropathology
- MeSH terms
- Alzheimer Disease, Humans, Amyloid beta-Peptides, tau Proteins, Tauopathies, Positron-Emission Tomography
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