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Evidence for Reduced Somatic T-Cell Receptor Sequence Diversity Profiles Among Midwestern Amish in an Aging Cohort Study
Cruz LA, Liu S, Miskimen KL, Cooke Bailey JN, Kinzy T, Song YE, Laux RA, Miron P et al.. Annals of human genetics, 2026-10-18
Topic: Brain proteins, microglia and lab models
The causes of late onset Alzheimer disease (LOAD) are not known but several recent lines of evidence implicate the adaptive immune system. To characterize the adaptive immune system among Midwestern Amish participating in longitudinal studies of aging. We immunosequenced the T-cell receptor (TCR) beta chain from genomic DNA of 72 participants, including those with clinically diagnosed LOAD (n = 6), mild cognitive impairment (MCI; n = 16), cognitive impairment but not AD (n = 3), and 35 cognitively unaffected. For a subset of participants, LOAD pathogenesis plasma biomarkers were available. TCR sequence diversity measured as Simpson's clonality was lower among LOAD+MCI compared with non-LOAD, but these differences were not independent of age. Relatively few clonotypes (exact nucleotide sequences) were shared across participants; of those few shared include the Epstein Barr virus associated clonotype. HLA-A*03:01 and several HLA-DRB1 alleles were under-represented among LOAD+MCI participants compared with cognitively unaffected participants, but these associations were no longer significant in adjusted analyses. Among LOAD+MCI participants, increased p-tau181 was nominally associated with decreased TCR sequence diversity, and the nominal association was independent of age; however, this association did not remain statistically significant after strict correction for multiple testing and the limited sample size precluded formal tests of heterogeneity. In this limited Midwestern Amish sample, the preliminary TCR diversity trends are consistent with the involvement of the adaptive immune system in LOAD.
Key findings
- TCR sequence diversity measured as Simpson's clonality was lower among LOAD+MCI compared with non-LOAD, but these differences were not independent of age.
- HLA-A*03:01 and several HLA-DRB1 alleles were under-represented among LOAD+MCI participants compared with cognitively unaffected participants, but these associations were no longer significant in adjusted analyses.
- Among LOAD+MCI participants, increased p-tau181 was nominally associated with decreased TCR sequence diversity, and the nominal association was independent of age; however, this association did not remain statistically significant after strict correction for multiple testing and the limited sample size precluded formal tests of heterogeneity.
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Study details
- Study designlongitudinal study
- Participants72
- Evidence strengthModerate
How this study scored 66/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same 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 and multi-centre collaboration, so those were left out: it earned 38 of the 58 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Annals of human genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 1 / 4 | 72 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 42892741) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 38 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 38 of the 58 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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APA 7th
Cruz, L. A., Liu, S., Miskimen, K. L., Cooke Bailey, J. N., Kinzy, T., Song, Y. E., et al. (2026). Evidence for Reduced Somatic T-Cell Receptor Sequence Diversity Profiles Among Midwestern Amish in an Aging Cohort Study. Annals of human genetics. https://doi.org/10.1111/ahg.70063
Vancouver
Cruz LA, Liu S, Miskimen KL, Cooke Bailey JN, Kinzy T, Song YE, et al. Evidence for Reduced Somatic T-Cell Receptor Sequence Diversity Profiles Among Midwestern Amish in an Aging Cohort Study. Annals of human genetics. 2026. doi:10.1111/ahg.70063. PMID: 42892741.
BibTeX
@article{cruz2026-42892741,
author = {Cruz, L. A. and Liu, S. and Miskimen, K. L. and Cooke Bailey, J. N. and Kinzy, T. and Song, Y. E. and Laux, R. A. and Miron, P. and others},
title = {{Evidence for Reduced Somatic T-Cell Receptor Sequence Diversity Profiles Among Midwestern Amish in an Aging Cohort Study}},
journal = {Annals of human genetics},
year = {2026},
doi = {10.1111/ahg.70063},
pmid = {42892741},
url = {https://doi.org/10.1111/ahg.70063}
}
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