Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease
Open accessAbstract
Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer’s disease. We studied 150 cognitively unimpaired participants and 100 patients with mild cognitive impairment in the Swedish BioFINDER study. P-tau217 was measured repeatedly for up to 6 years (median three samples per person, median time from first to last sample, 4.3 years). Preclinical (amyloid-β-positive cognitively unimpaired, n = 62) and prodromal (amyloid-β-positive mild cognitive impairment, n = 49) Alzheimer’s disease had accelerated p-tau217 compared to amyloid-β-negative cognitively unimpaired (β = 0.56, P < 0.001, using linear mixed effects models) and amyloid-β-negative mild cognitive impairment patients (β = 0.67, P < 0.001), respectively. Mild cognitive impairment patients who later converted to Alzheimer’s disease dementia (n = 40) had accelerated p-tau217 compared to other mild cognitive impairment patients (β = 0.79, P < 0.001). P-tau217 did not change in amyloid-β-negative participants, or in patients with mild cognitive impairment who did not convert to Alzheimer’s disease dementia. For 80% power, 109 participants per arm were required to observe a slope reduction in amyloid-β-positive cognitively unimpaired (71 participants per arm in amyloid-β-positive mild cognitive impairment). Longitudinal increases in p-tau217 correlated with longitudinal worsening of cognition and brain atrophy. In summary, plasma p-tau217 increases during early Alzheimer’s disease and can be used to monitor disease progression.
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Plasma ptau-217 changes are detectable in preclinical stages and predictive of progression to mild cognitive impairment and AD dementia in a dose-dependent relationship.
“These changes are detectable in preclinical stages and predictive of progression to mild cognitive impairment (MCI) and AD dementia in a dose-dependent relationship (16,23,27).”
From Amyloid-Independent Elevation of Plasma phosphorylated tau-217 Tracks Neurodegenerative Risk in Tuberous Sclerosis Complex: Implications for mTOR-Targeted Intervention (2026) · cites this paper as [23]
The Results (Longitudinal plasma p-tau217 in different diagnostic groups; page unavailable) show increasing p-tau217 in amyloid-β+ cognitively unimpaired participants and higher baseline levels in MCI patients who later developed Alzheimer’s disease dementia; a Cox analysis also links p-tau217 to dementia-conversion risk. The paper does not establish that p-tau217 predicts progression from the preclinical stage to MCI, or a dose-dependent relationship for progression through both MCI and dementia. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn CU, amyloid-negative AD populations, correlations between plasma ptau-217 and age are typically modest or absent (correlation coefficients ranging from 0.48 to -0.02).
“In CU, amyloid-negative AD populations, correlations between plasma ptau-217 and age are typically modest or absent (correlation coefficients ranging from 0.48 to -0.02), consistent with limited age-driven change (16,23,24).”
From Amyloid-Independent Elevation of Plasma phosphorylated tau-217 Tracks Neurodegenerative Risk in Tuberous Sclerosis Complex: Implications for mTOR-Targeted Intervention (2026) · cites this paper as [23]
The Results section (‘Longitudinal plasma p-tau217 in different diagnostic groups’; page unavailable) reports that plasma p-tau217 remained stable over time in amyloid-negative cognitively unimpaired participants, consistent with limited longitudinal change. It does not report correlations between p-tau217 and age or the claimed coefficients of 0.48 to −0.02; longitudinal stability is not itself an age-correlation estimate. (LLM, conf=0.78)
Experimental — accuracy not yet measuredAmyloid positivity in AD patients is associated with substantially accelerated increases in ptau-217, with prospective longitudinal studies demonstrating a six-fold higher annual increase in plasma ptau-217 in amyloid-positive versus amyloid-negative individuals.
“In contrast, amyloid positivity in AD patients is associated with substantially accelerated increases in ptau-217, with prospective longitudinal studies demonstrating a six-fold higher annual increase in plasma ptau-217 in amyloid-positive versus amyloid-negative individuals (16,23,26).”
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- Authors
- Mattsson-Carlgren, N., Janelidze, S., Palmqvist, S., Cullen, N., Svenningsson, A. L., Strandberg, O., Mengel, D., Walsh, D. M., Stomrud, E., Dage, J. L., & Hansson, O.
- Affiliations
- Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden
- Lund University (SE)
- Brigham and Women's Hospital (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Hansson, Oskar
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-10-17
- Volume
- 143
- Issue
- 11
- Pages
- 3234-3241
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC7719022
- OpenAlex
- W3092650901
- Cited by
- 368
- References
- 0
- Citations by year
- 2026: 94 · 2025: 80 · 2024: 62 · 2023: 36 · 2022: 49 · 2021: 45 · 2020: 1
- FWCI
- 24.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Brain (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Research Council
- Wallenberg Center for Molecular Medicine
- Knut and Alice Wallenberg foundation
- Medical Faculty at Lund University, Region Skåne
- Marianne and Marcus Wallenberg foundation
- Strategic Research Area MultiPark
- Lund University
- Swedish Alzheimer Foundation
- Swedish Brain Foundation
- Swedish Medical Association
- Konung Gustaf V: s och Drottning Victorias Frimurarestiftelse
- Bundy Academy
- Skåne University Hospital Foundation
- Alzheimer’s Association Zenith Fellow
- German Research Foundation (DFG ME 4858/1-1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- p-tau217, tau phosphorylation, Alzheimer's disease, mild cognitive impairment, amyloid-beta, preclinical Alzheimer's disease, prodromal Alzheimer's disease, plasma biomarkers, longitudinal biomarker changes, cognitive decline, brain atrophy, disease progression monitoring, conversion to dementia
- MeSH terms
- Mental Status and Dementia Tests, Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Phosphorylation, Prospective Studies, Threonine, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cognitive Dysfunction
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