Home › Research › How common it is
Fine-mapping HLA-II haplotypes in Alzheimer's disease and healthy longevity reveals distinct associations with microglial HLA-II load and neuropathology
Alvarez Sirvent, D.; Luimes, M. C.; Tesi, N.; Rohde, S. K.; Salazar, A. N.; Bijker, L. J.; van Schoor, N. M.; Tijms et al.. medRxiv (preprint), 2026-08-27
Topic: Amyloid, tau and blood-test diagnosis
Human leukocyte antigen (HLA) class II variation is implicated in Alzheimers disease (AD) and longevity, but its mechanisms within the major histocompatibility complex remain unclear. We fine-mapped seven independent HLA-II haplotypes in 6,053 individuals (443 cognitively healthy centenarians [CHCs], 3,219 population controls, 2,391 AD patients). Three haplotypes overlapped previous AD and lifespan signals. Hap-B (DRB1*04 subtypes) was protective, enriched in CHCs and controls versus AD, with its neuroprotective association with tau pathology replicated in an independent Netherlands Brain Bank cohort. Hap-R (DRB1*01:01) increased AD risk and reduced healthy longevity, with reduced microglial HLA-II activation. Hap-Y (DRB1*15:01) showed increased microglial HLA-II activation in post-mortem brain tissue, independent of quantitative AD neuropathology. These findings indicate distinct HLA-II haplotypes shape AD susceptibility and healthy longevity through separate mechanisms, linking HLA architecture to brain immune states beyond classical neuropathology.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Alvarez Sirvent, D., Luimes, M. C., Tesi, N., Rohde, S. K., Salazar, A. N., Bijker, L. J., et al. (2026). Fine-mapping HLA-II haplotypes in Alzheimer's disease and healthy longevity reveals distinct associations with microglial HLA-II load and neuropathology. medRxiv (preprint). https://doi.org/10.64898/2026.08.24.26361177
Vancouver
Alvarez Sirvent D, Luimes MC, Tesi N, Rohde SK, Salazar AN, Bijker LJ, et al. Fine-mapping HLA-II haplotypes in Alzheimer's disease and healthy longevity reveals distinct associations with microglial HLA-II load and neuropathology. medRxiv (preprint). 2026. doi:10.64898/2026.08.24.26361177.
BibTeX
@article{alvarezsirvent2026-5023ac4e,
author = {Alvarez Sirvent, D. and Luimes, M. C. and Tesi, N. and Rohde, S. K. and Salazar, A. N. and Bijker, L. J. and van Schoor, N. M. and Tijms and others},
title = {{Fine-mapping HLA-II haplotypes in Alzheimer's disease and healthy longevity reveals distinct associations with microglial HLA-II load and neuropathology}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.24.26361177},
url = {https://doi.org/10.64898/2026.08.24.26361177}
}
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.
Key findings
- Hap-B (DRB1*04 subtypes) was protective, enriched in CHCs and controls versus AD, with its neuroprotective association with tau pathology replicated in an independent Netherlands Brain Bank cohort.
- These findings indicate distinct HLA-II haplotypes shape AD susceptibility and healthy longevity through separate mechanisms, linking HLA architecture to brain immune states beyond classical neuropathology.
Why it matters
This fine-mapping study found distinct HLA-II haplotypes associated with Alzheimer's disease risk and healthy longevity, with one protective haplotype linked to tau pathology and others to microglial HLA-II activation. These genetic and immune findings may inform understanding of disease mechanisms, not treatment or cure.
New to this subject? Start with our plain-English guide: Alzheimer's in numbers →
Study details
- Participants6,053
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 29 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 27 of the 94 points we could judge it on, which is 29 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| 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 | 3 / 5 | Rated “moderate” 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 | 3 / 4 | 6,053 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Henne H. Holstege: h-index 43 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University Medical Center Groningen: institution h-index 995 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 27 of the 94 points we could judge it on is 29 out of 100. |
| Total | 29 / 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 →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in How common it is
Also tagged “precursor”
1,337 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,337 tagged studies.