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TDP‐43 and APOE: A complex interaction
Muhammad I. Abeer, Steven R. Boone, Michael A. Gitcho. Alzheimer s & Dementia, 2025-12-01
Topic: Brain proteins, microglia and lab models
We identified an interaction between TDP-43 and APOE through immunoprecipitation followed by proteomics in mice, verified in human brain by co- immunoprecipitation. In addition to that we identified a difference in post translational modifications of APOE between AD patients without TDP-43 pathology and LATE patients with TDP-43 pathology. We further show in a cellular model of APOE4 overexpression that endogenous TDP-43 interacts in complex with APOE4. In addition, primary mouse astrocytes challenged with oxidative stress show a significant increase in endogenous APOE/TDP-43 colocalization. Our results indicate a functional relationship between TDP-43 and APOE which could offer more insights into the pathology of these diseases.
Key findings
- We identified an interaction between TDP-43 and APOE through immunoprecipitation followed by proteomics in mice, verified in human brain by co- immunoprecipitation.
- In addition to that we identified a difference in post translational modifications of APOE between AD patients without TDP-43 pathology and LATE patients with TDP-43 pathology.
- We further show in a cellular model of APOE4 overexpression that endogenous TDP-43 interacts in complex with APOE4.
- In addition, primary mouse astrocytes challenged with oxidative stress show a significant increase in endogenous APOE/TDP-43 colocalization.
- Our results indicate a functional relationship between TDP-43 and APOE which could offer more insights into the pathology of these diseases.
Why it matters
This study found that TDP-43 and APOE interact in mice, human brain and a cellular model of APOE4 overexpression, and that APOE post-translational modifications differ between AD patients without TDP-43 pathology and LATE patients with TDP-43 pathology. It describes a functional relationship between the two proteins but does not test or establish any treatment, cure or prevention.
Study details
- Evidence strengthLow
How this study scored 31/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Michael A. Gitcho: h-index 17 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Delaware State University: institution h-index 127 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41443591) |
| Free to read | 2 / 2 | Free to read |
| Total | 31 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1002/alz70855_105886
- PubMed: 41443591
- Original source →
- Free full text: Alzheimer s & Dementia →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Abeer, M. I., Boone, S. R., & Gitcho, M. A. (2025). TDP‐43 and APOE: A complex interaction. Alzheimer s & Dementia. https://doi.org/10.1002/alz70855_105886
Vancouver
Abeer MI, Boone SR, Gitcho MA. TDP‐43 and APOE: A complex interaction. Alzheimer s & Dementia. 2025. doi:10.1002/alz70855_105886. PMID: 41443591.
BibTeX
@article{abeer2025-41443591,
author = {Abeer, Muhammad I. and Boone, Steven R. and Gitcho, Michael A.},
title = {{TDP‐43 and APOE: A complex interaction}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz70855_105886},
pmid = {41443591},
url = {https://doi.org/10.1002/alz70855_105886}
}