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Associations Between Changes in Levels of Phosphorylated Tau and Severity of Cognitive Impairment in Early Alzheimer Disease
Gonzalez-Ortiz F, Kirsebom BE, Yakoub Y, Gundersen JK, Pålhaugen L, Waterloo K, Selnes P, Jarholm JA et al.. Neurology, 2025-05-15
Topic: Amyloid, tau and blood-test diagnosis
Background and objectives Aligning biomarker evidence with clinical presentation in early Alzheimer disease (AD) is essential for improving diagnosis, prognosis, and interventions. This study evaluates the relationship between cognitive impairment, future decline, and phosphorylated tau levels in plasma and CSF in predementia AD. Methods This longitudinal observational study included predementia cases and controls from 2 independent cohorts: the Norwegian Dementia Disease Initiation (DDI) and Canadian Pre-Symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD). In DDI, cognitively normal (CN) and mild cognitive impairment (MCI) cases were classified using CSF Aβ42/40 ratio (A) and p-tau181 (T), whereas classification in PREVENT-AD (A) was based on amyloid PET scans. In DDI, we assessed CSF-plasma correlations for p-tau181, p-tau217, and p-tau231. Diagnostic accuracies were evaluated through receiver operating characteristic analyses. Linear mixed models evaluated p-tau associations with future memory decline. Between-group differences in plasma p-tau217 were assessed in both cohorts. Results In DDI (n = 431), participants were classified as CN A-/T- (n = 169), A+/T- (CN = 26, MCI = 24), A+/T+ (CN = 40, MCI = 105), and A-/T+ (CN = 34, MCI = 33), with a mean age of 64.1 years and 55.9% female. In PREVENT-AD (n = 190), participants were categorized as CN A- (n = 118), CN A+ (n = 49), and MCI A+ (n = 21), with a mean age of 67.8 years and 72.6% female. In DDI, plasma p-tau217 showed high accuracy in identifying A+ participants (areas under the curve [AUC]: 0.85) and a moderate correlation with CSF p-tau217 (rho = 0.65, p p p p p p Discussion Our findings suggest that, unlike p-tau181 and p-tau231, plasma p-tau217 consistently aligns with cognitive status in A+ individuals and better reflects CSF biomarker abnormalities, reducing discrepancies between clinical and biochemical findings. Its association with baseline and future memory decline highlights its diagnostic and prognostic value, particularly when CSF analysis or PET is unavailable.
Key findings
- Results In DDI (n = 431), participants were classified as CN A-/T- (n = 169), A+/T- (CN = 26, MCI = 24), A+/T+ (CN = 40, MCI = 105), and A-/T+ (CN = 34, MCI = 33), with a mean age of 64.1 years and 55.9% female.
- In DDI, plasma p-tau217 showed high accuracy in identifying A+ participants (areas under the curve [AUC]: 0.85) and a moderate correlation with CSF p-tau217 (rho = 0.65, p < 0.001).
Why it matters
In predementia Alzheimer's, plasma p-tau217 aligned well with amyloid status and memory decline, while p-tau181 and p-tau231 did not align as consistently. This is about improving diagnosis and prognosis with biomarkers, not about treating, curing, or preventing Alzheimer's.
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Study details
- Study designlongitudinal study
- Participants431
- Effect size55.9%; 72.6%
- Evidence strengthModerate
How this study scored 70/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 431 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 15 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 9.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kaj Blennow: h-index 220 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 19 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40373247) |
| Free to read | 2 / 2 | Free to read |
| Total | 70 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Gonzalez-Ortiz, F., Kirsebom, B. E., Yakoub, Y., Gundersen, J. K., Pålhaugen, L., Waterloo, K., et al. (2025). Associations Between Changes in Levels of Phosphorylated Tau and Severity of Cognitive Impairment in Early Alzheimer Disease. Neurology. https://doi.org/10.1212/wnl.0000000000213676
Vancouver
Gonzalez-Ortiz F, Kirsebom BE, Yakoub Y, Gundersen JK, Pålhaugen L, Waterloo K, et al. Associations Between Changes in Levels of Phosphorylated Tau and Severity of Cognitive Impairment in Early Alzheimer Disease. Neurology. 2025. doi:10.1212/wnl.0000000000213676. PMID: 40373247.
BibTeX
@article{gonzalezortiz2025-40373247,
author = {Gonzalez-Ortiz, F. and Kirsebom, B. E. and Yakoub, Y. and Gundersen, J. K. and Pålhaugen, L. and Waterloo, K. and Selnes, P. and Jarholm, J. A. and others},
title = {{Associations Between Changes in Levels of Phosphorylated Tau and Severity of Cognitive Impairment in Early Alzheimer Disease}},
journal = {Neurology},
year = {2025},
doi = {10.1212/wnl.0000000000213676},
pmid = {40373247},
url = {https://doi.org/10.1212/wnl.0000000000213676}
}
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