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Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits
Sewell KR, Oberlin LE, Karikari TK, Olvera-Rojas M, Wan L, Morris JK, Kueck PJ, Zeng X et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-03-01
Topic: Amyloid, tau and blood-test diagnosis
Introduction The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample. Methods Participants (n = 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (Aβ)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/Aβ1-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). Results Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = -0.11, SE = 0.04, p = .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217. Discussion Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD. Highlights There is heterogeneity in the causes of cognitive decline in aging. AD-related blood biomarkers may help characterize these causes. Elevated p-tau217 was exclusively associated with poorer episodic memory. Elevated NfL was associated with poorer cognition in a broad range of domains. Blood biomarkers may help differentiate AD- and non-AD-related cognitive deficits.
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APA 7th
Sewell, K. R., Oberlin, L. E., Karikari, T. K., Olvera-Rojas, M., Wan, L., Morris, J. K., et al. (2025). Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14619
Vancouver
Sewell KR, Oberlin LE, Karikari TK, Olvera-Rojas M, Wan L, Morris JK, et al. Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.14619. PMID: 40110626.
BibTeX
@article{sewell2025-40110626,
author = {Sewell, K. R. and Oberlin, L. E. and Karikari, T. K. and Olvera-Rojas, M. and Wan, L. and Morris, J. K. and Kueck, P. J. and Zeng, X. and others},
title = {{Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.14619},
pmid = {40110626},
url = {https://doi.org/10.1002/alz.14619}
}
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Key findings
- Introduction The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood.
- Results Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = -0.11, SE = 0.04, p = .003), and remained so after covarying for NfL.
- Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217.
- Discussion Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits.
- Elevated p-tau217 was exclusively associated with poorer episodic memory.
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Study details
- Participants648
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 648 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40110626) |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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