Evidence map›Paper›PMID 41646721›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Evidence for reduced somatic T-cell receptor sequence diversity profiles among Midwestern Amish in an aging cohort study.

Lauren A Cruz, Shiying Liu, Kristy L Miskimen, Jessica N Cooke Bailey, Tyler Kinzy, Yeunjoo E Song, Renee A Laux, Penelope Miron, Paula K Ogrocki, Alan J Lerner and 9 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Lauren A CruzDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Shiying LiuDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Kristy L MiskimenDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Jessica N Cooke BaileyEast Carolina University, Greenville, NC.
Tyler KinzyEast Carolina University, Greenville, NC.
Yeunjoo E SongDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Renee A LauxDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Penelope MironDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Paula K OgrockiDepartment of Neurology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Alan J LernerDepartment of Neurology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Audrey LynnDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Sarada L FuzzellDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Sherri D HochstetlerDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Ioanna KonidariThe Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida.
Jacob L McCauleyThe Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida.
William K ScottThe Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida.
Margaret A Pericak-VanceThe Dr. John T. Macdonald Foundation Department of Human Genetics, John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida.
Jonathan L HainesDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Dana C CrawfordDepartment of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio.ORCID 0000-0002-6437-6248

Funding

Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1M
Protective Genetic Variants for Alzheimer Disease in the AmishRF1AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI HAINES, JONATHAN L, PERICAK-VANCE, MARGARET A. · 2017 to 2019
$8.2M
Protective Genetic Varients for Alzheimer Disease in the AmishR01AG058066 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI Jonathan L Haines, Margaret A. Pericak-Vance · 2022 to 2026
$8.0M
BIOMETRIC-GENETIC ANALYSIS OF CARDIOVASCULAR DISEASET32HL007567 · NHLBI · LOUISIANA STATE UNIV HSC NEW ORLEANS · PI ZHU, XIAOFENG · 1985 to 2021
$6.0M
T-cell receptor repertoires and Alzheimer's diseaseR03AG063229 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI CRAWFORD, DANA C · 2019 to 2020
$321k
NCATS NIH HHS UM1 TR004528NHLBI NIH HHS T32 HL007567NIA NIH HHS R01 AG058066NIA NIH HHS R03 AG063229NIA NIH HHS RF1 AG058066
6 · The paper itself

Abstract

Late-onset Alzheimer disease (LOAD), the most common form of dementia among older adults, is a neurodegenerative disease characterized by brain amyloid-β (Aβ) plaque deposition and neurofibrillary tangles. The causes of LOAD are not known but several recent lines of evidence implicate the adaptive immune system. Here, we sought to characterize somatic T-cell receptor (TCR) sequence diversity profiles and class I and II human leukocyte antigen (HLA) alleles from DNA extracted from peripheral tissues from Midwestern Amish participating in longitudinal studies of aging. We immunosequenced the TCR beta chain from genomic DNA of 72 Midwestern Amish, including participants with clinically diagnosed LOAD (n=6), mild cognitive impairment (MCI; n=16), cognitive impairment but not AD (CINAD; n=3), and 35 cognitively unaffected. TCR sequence diversity by cognitive status was examined using a variety of metrics, and tests of association were performed between cognitive status and HLA alleles. For a subset of participants, plasma biomarkers for LOAD pathogenesis were available to evaluate TCR sequence diversity by cognitive status. 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 with plasma biomarkers, increased p-tau181 was associated decreased TCR sequence diversity, and the association was independent of age. In this limited Midwestern Amish sample, the observed TCR diversity associations are consistent with the involvement of the adaptive immune system in LOAD.

Indexed as

Adaptive ImmunityDementiaGeneticsHuman Leukocyte Antigen

Identifiers

PMID41646721
PMCPMC12870599

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.