Home › Research › Brain tissue and pathology
Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome
Suzanne S. M. Miedema, Ana Rajicic, Merel O. Mol, Iryna Paliukhovich, Remco V. Klaassen, Renee van Buuren, Ka Wan Li, Frank Koopmans et al.. Acta Neuropathologica Communications, 2025-07-25
Topic: Brain proteins, microglia and lab models
Semantic dementia (SD) is a clinical subtype of frontotemporal dementia characterized by impaired word comprehension and semantic memory, and occurs nearly always sporadically. Neuroimaging typically reveals asymmetric, predominantly left-sided, atrophy of the anterior temporal pole, anterior fusiform gyrus, and the hippocampus. Post-mortem pathological examination shows frontotemporal lobar degeneration TDP type C, characterized by long dystrophic neurites in the temporal cortex and typical round, TDP-43-positive neuronal inclusions in the dentate gyrus. While neuronal loss in the temporal cortex is severe in the end stage of disease, the dentate gyrus seems relatively spared. This characteristic and well-defined disease profile suggests SD patients share a specific underlying disease biology. Recently, we performed the first quantitative proteomic study of the dentate gyrus, uncovering potential SD-specific biological pathways. Here, we report on the first quantitative proteomic study of the temporal cortex in SD. We studied the same patient and non-demented control cohort, enabling comparative analysis between the two brain regions. In addition, we compared our dataset with other frontotemporal lobar degeneration subtypes and Alzheimer's disease to separate SD disease-specific changes from common neurodegenerative processes. In the temporal cortex, involvement of the ribonucleoprotein complex and presynaptic regulation of cytosolic calcium levels by voltage-gated calcium channels appear unique facets of the SD disease process. Furthermore, we observed a striking difference in the abundance of neuropathological proteins TDP-43 and ANXA11, and their interactors between the temporal cortex and dentate gyrus. The elucidation of these potentially unique disease-specific mechanisms improves our understanding of the pathophysiological processes in SD and paves the way for the discovery of novel therapeutic targets.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Miedema, S. S. M., Rajicic, A., Mol, M. O., Paliukhovich, I., Klaassen, R. V., van Buuren, R., et al. (2025). Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome. Acta Neuropathologica Communications. https://doi.org/10.1186/s40478-025-02077-x
Vancouver
Miedema SSM, Rajicic A, Mol MO, Paliukhovich I, Klaassen RV, van Buuren R, et al. Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome. Acta Neuropathologica Communications. 2025. doi:10.1186/s40478-025-02077-x. PMID: 40713859.
BibTeX
@article{miedema2025-40713859,
author = {Miedema, Suzanne S. M. and Rajicic, Ana and Mol, Merel O. and Paliukhovich, Iryna and Klaassen, Remco V. and van Buuren, Renee and Li, Ka Wan and Koopmans, Frank and others},
title = {{Proteomics of the temporal cortex in semantic dementia reveals brain-region specific molecular pathology and regulation of the TDP-43-ANXA11 interactome}},
journal = {Acta Neuropathologica Communications},
year = {2025},
doi = {10.1186/s40478-025-02077-x},
pmid = {40713859},
url = {https://doi.org/10.1186/s40478-025-02077-x}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Furthermore, we observed a striking difference in the abundance of neuropathological proteins TDP-43 and ANXA11, and their interactors between the temporal cortex and dentate gyrus.
Why it matters
This proteomic study of the temporal cortex in semantic dementia found a striking difference in the abundance of TDP-43 and ANXA11 and their interacting proteins between the temporal cortex and the dentate gyrus. This suggests the disease involves brain-region specific molecular changes rather than one uniform process.
Study details
- Evidence strengthModerate
How this study scored 41/100
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 (Acta Neuropathologica Communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 3 / 5 | Rated “moderate” 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 | 2 / 7 | Cited 5 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 2.8× 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 | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Cornelis Van Swieten: h-index 104 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Erasmus MC: institution h-index 1,321 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40713859) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s40478-025-02077-x
- PubMed: 40713859
- Original source →
- Free full text: Acta Neuropathologica Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Brain tissue and pathology
Also tagged “tdp-43”
1,150 studies in the library carry the topic tag “tdp-43”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,150 tagged studies.