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Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease.

Overview

Authors: Randy A. Grant1,2,3, Rachel L. Doser1,2,3, Thomas J. LaRocca1,2,3
ORCID iDs: Thomas J. LaRocca
  1. Department of Health & Exercise Science Colorado State University Fort Collins Colorado USA
  2. Center for Healthy Aging Colorado State University Fort Collins Colorado USA
  3. Molecular, Cellular, & Integrative Neuroscience Program Colorado State University Fort Collins Colorado USA
Institutions: Colorado State University (United States)
Journal: Aging cell, volume 25, issue 8, article e70653
Dates: received 1 December 2025; accepted 28 July 2026; published online 12 August 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1111/acel.70653 · PMID 42587389 · PMCID PMC13469183 · OpenAlex W7202382971
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Connectivity
MeSH: Aging*, Alzheimer Disease*, DNA Transposable Elements*, Microglia*, Aged, 80 and over, Animals, Female, Humans, Mice, Mice, Transgenic (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: NIH (AG078859)
Citations: not cited yet (Europe PMC); 111 references in the paper

Abstract

Microglia, the brain's resident immune cells, are transcriptionally diverse and highly dynamic, but during aging and disease they lose their transcriptomic flexibility and adopt a chronically activated state that is associated with neuroinflammation and pathology. An emerging transcriptomic process that is also increasingly implicated in brain aging, neuroinflammation, and disease is the dysregulation of transposable elements (TEs), repetitive genomic sequences with the potential to cause cellular stress/dysfunction. However, there are limited data on microglial TE transcript patterns in these contexts. Here, we analyzed multiple RNA‐seq datasets from isolated human and mouse microglia across aging, Alzheimer's disease (AD), and AD‐associated pathology. In contrast to previous observations based on whole‐brain tissue and other brain cell types, we found that microglial TE transcript levels remained relatively consistent throughout most of the human lifespan before increasing in late life. We also found that TE transcript levels in microglia from AD patients showed minimal changes compared to age‐matched controls, and in RNA‐seq analyses of transgenic AD mouse models we observed pathology‐associated TE transcript decreases. Subsequent analyses identified inverse associations between TE transcript levels and autophagy/lysosome‐related gene expression, and in vitro studies suggested that aging‐ and AD‐relevant stimuli, as well as pharmacological autophagy inhibition, modulate TE transcript expression in cultured human microglia. Together, these data provide novel insight into TE transcript dynamics in microglia, highlighting TE transcript patterns that differ from those observed in whole‐brain samples and other cell types in aging and AD.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Other data links

Data Availability Statement

The data that support the findings of this study are available in Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/. These data were derived from the following resources available in the public domain:—GSE99074, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99074‐GSE146639 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99074-GSE146639), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146639‐GSE125050 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146639-GSE125050), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE125050‐GSE131869 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE125050-GSE131869), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi‐GSE123467 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi-GSE123467), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123467‐GSE205569 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123467-GSE205569), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi.

Reproduced under the paper's license (CC BY), from the paper cited above.

RNA‐Seq Datasets and Availability

All RNA‐seq data used in this manuscript were generated in previously published studies and are available on the Gene Expression Omnibus (GEO). Datasets included: No Cognitive Impairment (NCI) Dataset 1: human microglia isolated from cognitively normal individuals during full body autopsy (total RNA, GSE99074 (Galatro et al. 2017)), AD Dataset 2: human microglia isolated from AD patients and cognitively normal age‐matched controls during autopsy (total RNA, GSE146639 (Alsema et al. 2020)), AD Dataset 3: human microglia isolated from frozen samples of AD patients and cognitively normal age‐matched controls (total RNA, GSE125050 (Srinivasan et al. 2020)), Mouse Dataset 1: microglia isolated from WT mice across lifespan (total RNA, GSE131869 (Gyoneva et al. 2019)), Mouse Dataset 2: microglia isolated from rTg4510 mice (total RNA, GSE123467 (Wang et al. 2018)), Mouse Dataset 3: microglia isolated from APP/PS1 mice (total RNA, GSE205569 (Yin et al. 2023)).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 10 MeSH terms, 1 funder, 110 references.

Cite

This paper

Grant, R. A., Doser, R. L., & LaRocca, T. J. (2026). Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease. Aging cell, 25(8), e70653. https://doi.org/10.1111/acel.70653

BibTeX

@article{grant2026distinct,
author = {Grant, Randy A. and Doser, Rachel L. and LaRocca, Thomas J.},
title = {{Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease}},
journal = {Aging cell},
year = {2026},
month = aug,
volume = {25},
number = {8},
pages = {e70653},
publisher = {Wiley},
issn = {1474-9718},
doi = {10.1111/acel.70653},
url = {https://doi.org/10.1111/acel.70653},
pmid = {42587389},
pmcid = {PMC13469183}
}

RIS

TY - JOUR
AU - Grant, Randy A.
AU - Doser, Rachel L.
AU - LaRocca, Thomas J.
TI - Distinct Transposable Element Transcript Patterns in Microglia Across Aging and Alzheimer's Disease
T2 - Aging cell
J2 - Aging Cell
PY - 2026
DA - 2026/08/01
VL - 25
IS - 8
SP - e70653
SN - 1474-9718
PB - Wiley
DO - 10.1111/acel.70653
UR - https://doi.org/10.1111/acel.70653
LA - en
ER -

CSL-JSON

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