Evidence map›Paper›PMID 40791717›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Integrative effects of Telomere Length, Epigenetic Age, and Mitochondrial DNA abundance in Alzheimer's Disease.

Shea J Andrews, Brendan A Mitchell, Tong Tong, Luke W Bonham, Alan E Renton, Xiaoling Zhang, Marina Sirota, Duygu Tosun, Kristine Yaffe

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. 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

9 authors.

Shea J AndrewsDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA, USA.ORCID 0000-0002-1921-9470
Brendan A MitchellDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Tong TongBioinformatics Program, Boston University, Boston, MA, USA.
Luke W BonhamDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Alan E RentonDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Xiaoling ZhangBioinformatics Program, Boston University, Boston, MA, USA.
Marina SirotaBakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Kristine YaffeDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA, USA.

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Biomedical Imaging for Clinician ScientistsT32EB001631 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI THOMAS M LINK · 2005 to 2026
$5.6M
Elucidating the causal associations underlying Alzheimer's diseaseR00AG070109 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDREWS, SHEA J · 2023 to 2025
$742k
Elucidating the causal associations underlying Alzheimer's diseaseK99AG070109 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ANDREWS, SHEA J · 2021 to 2022
$252k
NIA NIH HHS K99 AG070109NIA NIH HHS R00 AG070109NIA NIH HHS U01 AG024904NIBIB NIH HHS T32 EB001631
6 · The paper itself

Abstract

Background and Objectives: Biological age, reflecting the cumulative molecular and cellular damage such as telomere attrition, epigenetic alterations and mitochondrial dysfunction, may better capture age-related decline and Alzheimer's disease (AD) risk than chronological age. Most studies have focused on one measure of biological age and not investigated joint or interactive contributions to AD pathogenesis. Methods: We estimated blood-derived telomere length (TL) via qPCR, epigenetic age (DNAm age) using the CausAge clock, and mitochondrial DNA copy number (mtDNAcn) from whole genome sequencing in 640 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI; Age: 74.91±7.56, Female: 44.8%, Cognitively Unimpaired: 34.3%, Mild Cognitive Impairment: 52%, AD: 12.9%). Linear mixed-effects models examined the associations and interactions of these markers with cognitive decline for memory, executive function, language ability, visuospatial ability, and global cognition, while linear regression tested associations with cross-sectional AD biomarkers (CSF Aβ Results: Individually, TL and DNAm age, were not associated with cognition, CSF biomarkers, or neuroimaging outcomes, while higher mtDNAcn was associated with lower CSF tau and ptau Discussion: These findings suggest that increased mtDNAcn may act as a compensatory response to accelerated epigenetic aging and telomere attrition. Our results underscore the importance of evaluating the interplay among multiple biological aging markers when investigating AD pathogenesis.

Identifiers

PMID40791717
PMCPMC12338940

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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 OpenQuestion graph.