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Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay
Wang YT, Ashton NJ, Therriault J, Benedet AL, Macedo AC, Pola I, Aumont E, Di Molfetta G et al.. Brain communications, 2025-01-07
Topic: Amyloid, tau and blood-test diagnosis
Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau 181 , p-tau 217 and p-tau 231 ) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field. A novel proteomic technology-NUcleic acid Linked Immuno-Sandwich Assay (NULISA)-was developed to improve the sensitivity of traditional proximity ligation assays and offer a comprehensive outlook for 120 protein biomarkers in neurodegenerative diseases. Due to the relative novelty of the NULISA technology in quantifying Alzheimer's disease biomarkers, validation through comparisons with more established methods is required. The main objective of the current study was to determine the capability of p-tau variants quantified using NULISA for identifying abnormal amyloid-β and tau pathology. We assessed 397 participants [mean (standard deviation) age, 64.8 (15.7) years; 244 females (61.5%) and 153 males (38.5%)] from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort where participants had plasma measurements of p-tau 181 , p-tau 217 and p-tau 231 from NULISA and single molecule arrays immunoassays. Participants also underwent neuroimaging assessments, including structural MRI, amyloid-PET and tau-PET. Our findings suggest an excellent agreement between plasma p-tau variants quantified using NULISA and single molecule arrays immunoassays. Plasma p-tau 217 measured with NULISA shows excellent discriminative accuracy for abnormal amyloid-PET (area under the receiver operating characteristic curve = 0.918, 95% confidence interval = 0.883 to 0.953, P < 0.0001) and tau-PET (area under the receiver operating characteristic curve = 0.939; 95% confidence interval = 0.909 to 0.969, P < 0.0001). It also presents the capability for differentiating tau-PET staging. Validation of the NULISA-measured plasma biomarkers adds to the current analytical methods for Alzheimer's disease diagnosis, screening and staging and could potentially expedite the development of a blood-based biomarker panel.
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APA 7th
Wang, Y. T., Ashton, N. J., Therriault, J., Benedet, A. L., Macedo, A. C., Pola, I., et al. (2025). Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay. Brain communications. https://doi.org/10.1093/braincomms/fcaf004
Vancouver
Wang YT, Ashton NJ, Therriault J, Benedet AL, Macedo AC, Pola I, et al. Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay. Brain communications. 2025. doi:10.1093/braincomms/fcaf004. PMID: 39845736.
BibTeX
@article{wang2025-39845736,
author = {Wang, Y. T. and Ashton, N. J. and Therriault, J. and Benedet, A. L. and Macedo, A. C. and Pola, I. and Aumont, E. and Di Molfetta, G. and others},
title = {{Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay}},
journal = {Brain communications},
year = {2025},
doi = {10.1093/braincomms/fcaf004},
pmid = {39845736},
url = {https://doi.org/10.1093/braincomms/fcaf004}
}
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Key findings
- Our findings suggest an excellent agreement between plasma p-tau variants quantified using NULISA and single molecule arrays immunoassays.
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Study details
- Participants397
- Effect size61.5%; 38.5%
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty journal. Scored zero for study design 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 37 of the 58 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain communications) |
| 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 | 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 | 397 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 | — / 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 39845736) |
| Free to read | 2 / 2 | Free to read |
| Points | 37 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 37 of the 58 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
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