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Neuropathologic correlates of distinct plasma biomarker profiles in community-living older adults
Lei Yu, Lianlian Du, Tianhao Wang, Lisa L Barnes, Jeffrey L Dage, Kristen A Russ, Tatiana Foroud, David A Bennett et al.. Brain : a journal of neurology, 2025-09-03
Topic: Plasma and spinal-fluid biomarkers
There has been a rapid growth in research on peripheral fluid biomarkers for Alzheimer's disease (AD) and AD-related dementias, because they are non-invasive, relatively inexpensive and easily accessible. The most commonly used plasma biomarkers include amyloid-β (Aβ), phosphorylated tau (p-tau), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). The extent to which distinct profiles of multiple plasma biomarkers correlate with common neuropathologies is unclear. Using clinicopathologic data from 405 community-dwelling older adults, we applied latent profile analysis to four plasma biomarkers, i.e. Aβ42/40 ratio, p-tau217, NfL and GFAP, and examined the correlates of the latent profiles with four degeneration measures: AD, Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy (LATE) and hippocampal sclerosis; and five vascular measures: chronic macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis and arteriosclerosis. On average, participants died at the age of 89, and blood samples for plasma biomarkers were measured 3.9 years before death. Over 75% were female, and 24% were non-Latino Black. We observed three distinct biomarker profiles. Profile 1, characterized by low p-tau217, low GFAP, low NfL and high Aβ42/40, represented most participants (55.6%), with better than average biomarker levels. Both Profile 2 and Profile 3 showed worse than average biomarker levels. Profile 2, representing 34.8% of the participants, was high in p-tau217 and GFAP. In contrast, Profile 3, representing 9.6% of the participants, was high in NfL and GFAP. Examination of neuropathologic correlates of these plasma biomarker profiles revealed that Profile 2 exemplifies older adults with a high burden of neurodegeneration; almost all participants (92.9%) in Profile 2 had a diagnosis of pathologic AD, and the group also had the highest percentage of participants with Lewy bodies (41.1%). In comparison, Profile 3 exemplifies older adults with more severe vascular conditions; participants in this group had the highest percentage of macroscopic infarcts (31.6%) and moderate or severe atherosclerosis (42.1%). Together, these findings suggest that common plasma biomarkers may exhibit profiles reflective of distinct pathophysiologic processes.
Key findings
- We observed three distinct biomarker profiles.
- Examination of neuropathologic correlates of these plasma biomarker profiles revealed that Profile 2 exemplifies older adults with a high burden of neurodegeneration; almost all participants (92.9%) in Profile 2 had a diagnosis of pathologic AD, and the group also had the highest percentage of participants with Lewy bodies (41.1%).
- Together, these findings suggest that common plasma biomarkers may exhibit profiles reflective of distinct pathophysiologic processes.
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Study details
- Effect size55.6%; 34.8%; 9.6%
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people 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, multi-centre collaboration and free to read, so those were left out: it earned 28 of the 56 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 40465828) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 28 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 28 of the 56 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
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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
Yu, L., Du, L., Wang, T., Barnes, L. L., Dage, J. L., Russ, K. A., et al. (2025). Neuropathologic correlates of distinct plasma biomarker profiles in community-living older adults. Brain : a journal of neurology. https://doi.org/10.1093/brain/awaf211
Vancouver
Yu L, Du L, Wang T, Barnes LL, Dage JL, Russ KA, et al. Neuropathologic correlates of distinct plasma biomarker profiles in community-living older adults. Brain : a journal of neurology. 2025. doi:10.1093/brain/awaf211. PMID: 40465828.
BibTeX
@article{yu2025-40465828,
author = {Yu, Lei and Du, Lianlian and Wang, Tianhao and Barnes, Lisa L and Dage, Jeffrey L and Russ, Kristen A and Foroud, Tatiana and Bennett, David A and others},
title = {{Neuropathologic correlates of distinct plasma biomarker profiles in community-living older adults}},
journal = {Brain : a journal of neurology},
year = {2025},
doi = {10.1093/brain/awaf211},
pmid = {40465828},
url = {https://doi.org/10.1093/brain/awaf211}
}
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