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Ultra-sensitive Mapping of Cell-free DNA-derived Methylomes Reveals Brain-specific Epigenetic Alterations Implicated in Alzheimer’s Disease
Cui X, Beadell AV, Tasaki S, Capuano AW, Zhang Z, Gao L, Chiu BC, He C et al.. medRxiv, 2026-10-26
Topic: Genetics and APOE
DNA cytosine modifications play a crucial role in gene regulation that underlies the pathogenesis of complex diseases such as Alzheimer’s disease (AD). Using LABS ( L inear A mplification-based B isulfite S equencing), an ultra-sensitive linear amplification-based low-input whole-genome methylation profiling method, we demonstrated the feasibility of detecting altered methylation features in serum-derived cell-free DNA (cfDNA) between a set of age- and sex-matched pathologically-defined participants with AD and non-AD controls, from the Rush Memory and Aging Project. These blood methylation changes were further linked to brain-specific epigenetic alterations implicated in AD. These findings support cfDNA methylome profiling as a promising non-invasive tool for AD biomarker discovery and research.
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APA 7th
Cui, X., Beadell, A. V., Tasaki, S., Capuano, A. W., Zhang, Z., Gao, L., et al. (2026). Ultra-sensitive Mapping of Cell-free DNA-derived Methylomes Reveals Brain-specific Epigenetic Alterations Implicated in Alzheimer’s Disease. medRxiv. https://doi.org/10.64898/2026.10.24.26366278
Vancouver
Cui X, Beadell AV, Tasaki S, Capuano AW, Zhang Z, Gao L, et al. Ultra-sensitive Mapping of Cell-free DNA-derived Methylomes Reveals Brain-specific Epigenetic Alterations Implicated in Alzheimer’s Disease. medRxiv. 2026. doi:10.64898/2026.10.24.26366278.
BibTeX
@article{cui2026-a5be5a37,
author = {Cui, X. and Beadell, A. V. and Tasaki, S. and Capuano, A. W. and Zhang, Z. and Gao, L. and Chiu, B. C. and He, C. and others},
title = {{Ultra-sensitive Mapping of Cell-free DNA-derived Methylomes Reveals Brain-specific Epigenetic Alterations Implicated in Alzheimer’s Disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.24.26366278},
url = {https://doi.org/10.64898/2026.10.24.26366278}
}
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Key findings
- Using LABS ( L inear A mplification-based B isulfite S equencing), an ultra-sensitive linear amplification-based low-input whole-genome methylation profiling method, we demonstrated the feasibility of detecting altered methylation features in serum-derived cell-free DNA (cfDNA) between a set of age- and sex-matched pathologically-defined participants with AD and non-AD controls, from the Rush Memory and Aging Project.
- These findings support cfDNA methylome profiling as a promising non-invasive tool for AD biomarker discovery and research.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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