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Postmortem Associations Between Alzheimer Disease Pathology and Plasma pTau217, GFAP, and NfL in AD and AD-Related Dementias
Pia Kivisäkk, Hadia A. Fatima, Chao‐Yi Wu, Nikhil Padmanabhan, Daniel Romero, Taron Gorham, Molly Weik, Hiroko H. Dodge et al.. Neurology, 2026-01-29
Topic: Amyloid, tau and blood-test diagnosis
One hundred eighty-seven participants with brain autopsy (NPDx1: AD n = 85; other n = 102; mean age: 74.3 years, 38.5% female; interval blood collection-death [mean ± SD]: 2.8 ± 1.6 years) and 67 NC without brain autopsy (mean age: 66.5 years, 71.6% female) were included. pTau217, but not GFAP, levels increased stepwise with increasing Thal phases (β = 0.61; 95% CI [0.24-0.97] to β = 0.91 [0.55-1.27]) and Braak stages (β = 0.59; [0.16-1.01] to β = 0.74 [0.33-1.15]). Although 23% of individuals with a non-AD NPDx1 had increased pTau217 levels using a cutoff defined by the contrast between ADNC and NC, the majority (62%) had intermediate/high ADNC copathology and the remaining pTau217+ individuals had borderline increased levels. By contrast, 48% of individuals without ADNC had increased GFAP levels. pTau217 and GFAP were not different in the presence or absence of cerebral amyloid angiopathy, α-synuclein or TDP-43 proteinopathies, or primary tauopathies. NfL was not specifically associated with ADNC. Plasma pTau217, but not GFAP or NfL, levels accurately reflect the presence of ADNC in the brain even in individuals with an NPDx1 of a non-AD dementia. Thus, a positive plasma pTau217 test in an individual with a suspected non-AD dementia should not necessarily be considered a misdiagnosis of the presumed non-AD dementia or as a false positive, but rather as evidence of ADNC copathology.
Key findings
- One hundred eighty-seven participants with brain autopsy (NPDx1: AD n = 85; other n = 102; mean age: 74.3 years, 38.5% female; interval blood collection-death [mean ± SD]: 2.8 ± 1.6 years) and 67 NC without brain autopsy (mean age: 66.5 years, 71.6% female) were included. pTau217, but not GFAP, levels increased stepwise with increasing Thal phases (β = 0.61; 95% CI [0.24-0.97] to β = 0.91 [0.55-1.27]) and Braak stages (β = 0.59; [0.16-1.01] to β = 0.74 [0.33-1.15]).
- Although 23% of individuals with a non-AD NPDx1 had increased pTau217 levels using a cutoff defined by the contrast between ADNC and NC, the majority (62%) had intermediate/high ADNC copathology and the remaining pTau217+ individuals had borderline increased levels.
- By contrast, 48% of individuals without ADNC had increased GFAP levels. pTau217 and GFAP were not different in the presence or absence of cerebral amyloid angiopathy, α-synuclein or TDP-43 proteinopathies, or primary tauopathies.
- NfL was not specifically associated with ADNC.
- Plasma pTau217, but not GFAP or NfL, levels accurately reflect the presence of ADNC in the brain even in individuals with an NPDx1 of a non-AD dementia.
Why it matters
In this autopsy cohort, plasma pTau217 reflected Alzheimer disease brain pathology even in people with other dementia diagnoses, while GFAP and NfL did not specifically track it. This supports pTau217 as a diagnostic marker, but it does not address treating, curing or preventing the disease.
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Study details
- Study designcohort study
- Participants85
- Effect size38.5%; 71.6%
- Evidence strengthModerate
How this study scored 66/100
Published in a leading specialty journal, and it is a cohort study following 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 cohort study following 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 85 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 | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 33.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Steven Edward Arnold: h-index 125 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41610380) |
| Free to read | 2 / 2 | Free to read |
| Total | 66 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000214351
- PubMed: 41610380
- Original source →
- Free full text: PubMed Central →
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
Kivisäkk, P., Fatima, H. A., Wu, C., Padmanabhan, N., Romero, D., Gorham, T., et al. (2026). Postmortem Associations Between Alzheimer Disease Pathology and Plasma pTau217, GFAP, and NfL in AD and AD-Related Dementias. Neurology. https://doi.org/10.1212/wnl.0000000000214351
Vancouver
Kivisäkk P, Fatima HA, Wu C, Padmanabhan N, Romero D, Gorham T, et al. Postmortem Associations Between Alzheimer Disease Pathology and Plasma pTau217, GFAP, and NfL in AD and AD-Related Dementias. Neurology. 2026. doi:10.1212/wnl.0000000000214351. PMID: 41610380.
BibTeX
@article{kivisakk2026-41610380,
author = {Kivisäkk, Pia and Fatima, Hadia A. and Wu, Chao‐Yi and Padmanabhan, Nikhil and Romero, Daniel and Gorham, Taron and Weik, Molly and Dodge, Hiroko H. and others},
title = {{Postmortem Associations Between Alzheimer Disease Pathology and Plasma pTau217, GFAP, and NfL in AD and AD-Related Dementias}},
journal = {Neurology},
year = {2026},
doi = {10.1212/wnl.0000000000214351},
pmid = {41610380},
url = {https://doi.org/10.1212/wnl.0000000000214351}
}
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