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Targeted proteomic biomarker profiling using NULISA in a cohort enriched with risk for Alzheimer's disease and related dementias
Ramiro Eduardo Rea Reyes, Rachael E. Wilson, Rebecca E. Langhough, Rachel L. Studer, Erin McMullen Jonaitis, Julie Elisabeth Oomens, Elizabeth M. Planalp, Barbara B. Bendlin et al.. Alzheimer s & Dementia, 2025-05-01
Topic: Amyloid, tau and blood-test diagnosis
-fold changes of 1.21, 0.57, and 4.63, respectively, compared to A-. Of interest, TAR DNA-binding protein 43 (TDP-43) phosphorylated at serine 409 (pTDP43-409) was also upregulated in the impaired group and correlated with declining hippocampal volume and cognitive trajectories. This study shows the potential of a targeted proteomics panel for characterizing brain changes pertinent to ADRD. The promising pTDP43-409 findings require further replication. HIGHLIGHTS: The NULISAseq pTau217 assay was comparable to the Simoa pTau217 assay, both utilizing the ALZpath antibody, in detecting amyloid positron emission tomography (PET) positivity, each with areas under the curve greater than 90%. Nineteen proteins were differentially expressed in participants with mild cognitive impairment (MCI) compared to those who were unimpaired. Markers of non-AD proteinopathies such as pTDP43-409, oligomeric alpha-synuclein, and huntingtin (HTT), were among those upregulated in MCI. High levels of plasma pTDP43-409 were associated with worsening hippocampal atrophy and cognitive decline, clinical indicators of limbic-predominant age-related TDP-43 encephalopathy (LATE), compared to those with low pTDP43-409.
Key findings
- -fold changes of 1.21, 0.57, and 4.63, respectively, compared to A-.
- Of interest, TAR DNA-binding protein 43 (TDP-43) phosphorylated at serine 409 (pTDP43-409) was also upregulated in the impaired group and correlated with declining hippocampal volume and cognitive trajectories.
- This study shows the potential of a targeted proteomics panel for characterizing brain changes pertinent to ADRD.
- The promising pTDP43-409 findings require further replication.
- HIGHLIGHTS: The NULISAseq pTau217 assay was comparable to the Simoa pTau217 assay, both utilizing the ALZpath antibody, in detecting amyloid positron emission tomography (PET) positivity, each with areas under the curve greater than 90%.
Why it matters
A targeted proteomics panel detected proteins linked to Alzheimer's and related dementias, including pTDP43-409, which correlated with declining hippocampal volume and cognitive trajectories. The authors state that the promising pTDP43-409 findings require further replication.
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Study details
- Study designcross-sectional
- Participants252
- Evidence strengthLow
How this study scored 58/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 252 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 | 3 / 7 | Cited 29 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 18.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Sterling C. Johnson: h-index 112 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40318118) |
| Free to read | 2 / 2 | Free to read |
| Total | 58 / 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
Reyes, R. E. R., Wilson, R. E., Langhough, R. E., Studer, R. L., Jonaitis, E. M., Oomens, J. E., et al. (2025). Targeted proteomic biomarker profiling using NULISA in a cohort enriched with risk for Alzheimer's disease and related dementias. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70166
Vancouver
Reyes RER, Wilson RE, Langhough RE, Studer RL, Jonaitis EM, Oomens JE, et al. Targeted proteomic biomarker profiling using NULISA in a cohort enriched with risk for Alzheimer's disease and related dementias. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70166. PMID: 40318118.
BibTeX
@article{reyes2025-40318118,
author = {Reyes, Ramiro Eduardo Rea and Wilson, Rachael E. and Langhough, Rebecca E. and Studer, Rachel L. and Jonaitis, Erin McMullen and Oomens, Julie Elisabeth and Planalp, Elizabeth M. and Bendlin, Barbara B. and others},
title = {{Targeted proteomic biomarker profiling using NULISA in a cohort enriched with risk for Alzheimer's disease and related dementias}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70166},
pmid = {40318118},
url = {https://doi.org/10.1002/alz.70166}
}
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