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TDP-43 Pathology in Alzheimer's Disease
Meneses A, Koga S, O'Leary J, Dickson DW, Bu G, Zhao N.. Molecular neurodegeneration, 2021-12-20
Topic: Amyloid, tau and blood-test diagnosis
Transactive response DNA binding protein of 43 kDa (TDP-43) is an intranuclear protein encoded by the TARDBP gene that is involved in RNA splicing, trafficking, stabilization, and thus, the regulation of gene expression. Cytoplasmic inclusion bodies containing phosphorylated and truncated forms of TDP-43 are hallmarks of amyotrophic lateral sclerosis (ALS) and a subset of frontotemporal lobar degeneration (FTLD). Additionally, TDP-43 inclusions have been found in up to 57% of Alzheimer's disease (AD) cases, most often in a limbic distribution, with or without hippocampal sclerosis. In some cases, TDP-43 deposits are also found in neurons with neurofibrillary tangles. AD patients with TDP-43 pathology have increased severity of cognitive impairment compared to those without TDP-43 pathology. Furthermore, the most common genetic risk factor for AD, apolipoprotein E4 (APOE4), is associated with increased frequency of TDP-43 pathology. These findings provide strong evidence that TDP-43 pathology is an integral part of multiple neurodegenerative conditions, including AD. Here, we review the biology and pathobiology of TDP-43 with a focus on its role in AD. We emphasize the need for studies on the mechanisms that lead to TDP-43 pathology, especially in the setting of age-related disorders such as AD.
Key findings
- AD patients with TDP-43 pathology have increased severity of cognitive impairment compared to those without TDP-43 pathology.
- Furthermore, the most common genetic risk factor for AD, apolipoprotein E4 (APOE4), is associated with increased frequency of TDP-43 pathology.
- These findings provide strong evidence that TDP-43 pathology is an integral part of multiple neurodegenerative conditions, including AD.
Why it matters
This review reports that TDP-43 inclusions are found in up to 57% of Alzheimer's disease cases and are associated with more severe cognitive impairment. It does not test any treatment or prevention, so it has no direct implications for treating, curing, or preventing Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 56/100
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 (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (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 | 3 / 5 | 2021 — within 6 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 | 6 / 7 | Cited 365 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 52.1 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 22.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 32 other studies in this library |
| Still being cited | 4 / 4 | Cited 278 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Na Zhao: h-index 40 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34930382) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-021-00503-x
- PubMed: 34930382
- Original source →
- Free full text: Molecular Neurodegeneration →
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
Meneses, A., Koga, S., O'Leary, J., Dickson, D. W., Bu, G., & Zhao, N. (2021). TDP-43 Pathology in Alzheimer's Disease. Molecular neurodegeneration. https://doi.org/10.1186/s13024-021-00503-x
Vancouver
Meneses A, Koga S, O'Leary J, Dickson DW, Bu G, Zhao N. TDP-43 Pathology in Alzheimer's Disease. Molecular neurodegeneration. 2021. doi:10.1186/s13024-021-00503-x. PMID: 34930382.
BibTeX
@article{meneses2021-34930382,
author = {Meneses, A. and Koga, S. and O'Leary, J. and Dickson, D. W. and Bu, G. and Zhao, N.},
title = {{TDP-43 Pathology in Alzheimer's Disease}},
journal = {Molecular neurodegeneration},
year = {2021},
doi = {10.1186/s13024-021-00503-x},
pmid = {34930382},
url = {https://doi.org/10.1186/s13024-021-00503-x}
}
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