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Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer’s risk- enhanced sample

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Du, Lianlian, Langhough, Rebecca E., Wilson, Rachael E., Reyes, Ramiro Eduardo Rea, Hermann, Bruce P., Jonaitis, Erin M., Betthauser, Tobey J., Chin, Nathaniel A. +10 more·2024·Alzheimer's & Dementia
DOI 10.1002/alz.14100PMC PMC11497664
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Abstract

INTRODUCTION: Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD). METHODS: Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated‐tau217 (p‐tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.6% with known amyloid status were amyloid positive (A+); 97.2% were cognitively unimpaired (CU). RESULTS: In the CU, amyloid‐negative (A–) subset, plasma p‐tau217 levels increased modestly with age but were unaffected by body mass index and kidney function. In the whole sample, average p‐tau217 change rates were higher in those who were A+ (e.g., simple slopes(se) for A+ and A– at age 60 were 0.232(0.028) and 0.038(0.013))). High baseline p‐tau217 levels predicted faster preclinical cognitive decline. DISCUSSION: p‐tau217 stands out among markers for its strong association with disease and cognitive decline, indicating its potential for early AD detection and monitoring progression. Highlights: Phosphorylated‐tau217 (p‐tau217) trajectories were significantly different in people who were known to be amyloid positive. Subtle age‐related trajectories were seen for all the plasma markers in amyloid‐negative cognitively unimpaired. Kidney function and body mass index were not associated with plasma p‐tau217 trajectories. Higher plasma p‐tau217 was associated with faster preclinical cognitive decline.

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  • 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).

    “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 [24]

    The Discussion (Aim 1: amyloid-negative CU controls) reports a modest but significant age-related increase in plasma p-tau217, supporting limited age-driven change in this group. The Results (Aim 1) likewise report significant age terms, but give regression estimates rather than the claimed correlation-coefficient range of 0.48 to −0.02; this paper does not support describing its observed association as absent. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Plasma ptau-217 has repeatedly demonstrated strong prognostic performance and generally outperforms other plasma biomarkers in predicting conversion from MCI to dementia.

    “Plasma ptau-217 has repeatedly demonstrated strong prognostic performance and generally outperforms other plasma biomarkers in predicting conversion from MCI to dementia (20,24).”

    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 [24]

    The Discussion (Aim 3; page unavailable) reports that p-tau217 had the strongest associations with cognitive decline among the plasma biomarkers studied. The Methods (Statistical analyses; page unavailable) specify that this analysis began with cognitively unimpaired participants and examined cognitive trajectories, not conversion from MCI to dementia. The paper therefore supports the broader prognostic comparison but not the claimed MCI-to-dementia outcome. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Du, L., Langhough, R. E., Wilson, R. E., Reyes, R. E. R., Hermann, B. P., Jonaitis, E. M., Betthauser, T. J., Chin, N. A., Christian, B., Chaby, L., Jeromin, A., Molfetta, G. D., Brum, W. S., Arslan, B., Ashton, N., Blennow, K., Zetterberg, H., & Johnson, S. C.
Affiliations
  • University of Wisconsin–Madison (US)
  • ALZpath, Inc. Carlsbad California USA
  • University of Gothenburg (SE)
  • Universidade Federal do Rio Grande do Sul (BR)
  • University of Science and Technology of China (CN)
Corresponding author
Johnson, Sterling C.
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2024-07-05
Volume
20
Issue
9
Pages
6183-6204
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.14100
PMC
PMC11497664
OpenAlex
W4400388912
Cited by
46
References
11
Citations by year
2026: 19 · 2025: 23 · 2024: 4
FWCI
13.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
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
phosphorylated tau217, plasma biomarkers
MeSH terms
Aged, Alzheimer Disease, Female, Humans, Longitudinal Studies, Male, Middle Aged, Phosphorylation, Biomarkers, tau Proteins, Disease Progression, Cognitive Dysfunction

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