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Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing
Christopher R S Belder, Amanda J Heslegrave, Owen Swann, Emily Abel, Millie Beament, Moneeb Nasir, Helen Rice, Philip S J Weston et al.. Journal of neurology, neurosurgery, and psychiatry, 2026-10-13
Topic: Plasma and spinal-fluid biomarkers
Nine proteins (amyloid-beta 42 (Aβ42), beta-secretase 1 (BACE1), glial fibrillary acidic protein (GFAP), pTau181, pTau231, pTau217, t0tal tau (MAPT), neurofilament light (NfL) and acetylcholinesterase (AChE)) robustly differed between carriers and non-carriers cross-sectionally. Longitudinal analyses showed elevated Aβ42 levels were statistically discernible in carriers approximately 26 years before expected symptom onset. Carriers diverged from non-carriers in phosphorylated tau markers at approximately 21–24 years before expected symptom onset, total tau at 19 years, GFAP and BACE1 at 14 years and NfL at 6 years. Differences in AChE were seen in symptomatic individuals likely reflecting cholinesterase inhibitor use. Multiple plasma proteins are elevated in presymptomatic and symptomatic ADAD mutation carriers relative to non-carriers. Changes in eight biomarkers occur sequentially from 26 to 6 years prior to symptom onset. Combining biomarkers may help in staging presymptomatic AD and optimise clinical trial inclusion. Further work is needed to assess how these findings generalise to non-monogenic AD.
Key findings
- Nine proteins (amyloid-beta 42 (Aβ42), beta-secretase 1 (BACE1), glial fibrillary acidic protein (GFAP), pTau181, pTau231, pTau217, t0tal tau (MAPT), neurofilament light (NfL) and acetylcholinesterase (AChE)) robustly differed between carriers and non-carriers cross-sectionally.
- Longitudinal analyses showed elevated Aβ42 levels were statistically discernible in carriers approximately 26 years before expected symptom onset.
- Carriers diverged from non-carriers in phosphorylated tau markers at approximately 21–24 years before expected symptom onset, total tau at 19 years, GFAP and BACE1 at 14 years and NfL at 6 years.
- Differences in AChE were seen in symptomatic individuals likely reflecting cholinesterase inhibitor use.
- Multiple plasma proteins are elevated in presymptomatic and symptomatic ADAD mutation carriers relative to non-carriers.
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Study details
- Study designcohort study
- Participants113
- Evidence strengthModerate
How this study scored 70/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for 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, multi-centre collaboration and free to read, so those were left out: it earned 39 of the 56 points we could judge it on, which is 70 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2 / 4 | 113 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 42637536) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 39 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 39 of the 56 points we could judge it on is 70 out of 100. |
| Total | 70 / 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
Belder, C. R. S., Heslegrave, A. J., Swann, O., Abel, E., Beament, M., Nasir, M., et al. (2026). Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp-2026-339037
Vancouver
Belder CRS, Heslegrave AJ, Swann O, Abel E, Beament M, Nasir M, et al. Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing. Journal of neurology, neurosurgery, and psychiatry. 2026. doi:10.1136/jnnp-2026-339037. PMID: 42637536.
BibTeX
@article{belder2026-42637536,
author = {Belder, Christopher R S and Heslegrave, Amanda J and Swann, Owen and Abel, Emily and Beament, Millie and Nasir, Moneeb and Rice, Helen and Weston, Philip S J and others},
title = {{Presymptomatic plasma biomarkers in autosomal dominant Alzheimer's disease: sequence and timing}},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2026},
doi = {10.1136/jnnp-2026-339037},
pmid = {42637536},
url = {https://doi.org/10.1136/jnnp-2026-339037}
}