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Loss and microglia phagocytosis of synaptic proteins in frontotemporal lobar degeneration with TDP-43 proteinopathy
Ivan Ayala, Atousa Bahrami, Yuting Pan, Callen Spencer, Margaret E Flanagan, M-Marsel Mesulam, Tamar Gefen, Changiz Geula. Neurochemistry international, 2024-03-05
Topic: Disease mechanisms in lab and animal studies
Cortical synaptic loss has emerged as an early abnormality in Alzheimer's disease (AD) with a strong relationship to cognitive performance. However, the status of synapses in frontotemporal lobar degeneration (FTLD) has received meager experimental attention. The purpose of this study was to investigate changes in cortical synaptic proteins in FTLD with tar DNA binding protein-43 (TDP-43) proteinopathy. A second aim was to study phagocytosis of synaptic proteins by microglia as a surrogate for synaptic pruning. Western blot analysis in frozen tissue from the middle frontal gyrus revealed decreased levels of the presynaptic protein synaptophysin, but slightly increased levels of the postsynaptic density protein 95 (PSD95) in FTLD-TDP. Levels of the dendritic spine protein spinophilin displayed the largest decrease. Double immunofluorescent staining visualized aggregate or punctate synaptic protein immunoreactivity in microglia. Overall, the proportion of microglia containing synaptic proteins was larger in FTLD-TDP when compared with normal controls. The increase in PSD95 levels may represent reactive upregulation of this protein, as suggested in AD. While greater numbers of microglia containing synaptic proteins is consistent with loss of synapses in FTLD-TDP, it may also be an indication of abnormal synaptic pruning by microglia.
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APA 7th
Ayala, I., Bahrami, A., Pan, Y., Spencer, C., Flanagan, M. E., Mesulam, M.-M., et al. (2024). Loss and microglia phagocytosis of synaptic proteins in frontotemporal lobar degeneration with TDP-43 proteinopathy. Neurochemistry international. https://doi.org/10.1016/j.neuint.2024.105719
Vancouver
Ayala I, Bahrami A, Pan Y, Spencer C, Flanagan ME, Mesulam M.-M, et al. Loss and microglia phagocytosis of synaptic proteins in frontotemporal lobar degeneration with TDP-43 proteinopathy. Neurochemistry international. 2024. doi:10.1016/j.neuint.2024.105719. PMID: 38452814.
BibTeX
@article{ayala2024-38452814,
author = {Ayala, Ivan and Bahrami, Atousa and Pan, Yuting and Spencer, Callen and Flanagan, Margaret E and Mesulam, M-Marsel and Gefen, Tamar and Geula, Changiz},
title = {{Loss and microglia phagocytosis of synaptic proteins in frontotemporal lobar degeneration with TDP-43 proteinopathy}},
journal = {Neurochemistry international},
year = {2024},
doi = {10.1016/j.neuint.2024.105719},
pmid = {38452814},
url = {https://doi.org/10.1016/j.neuint.2024.105719}
}
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Key findings
- Western blot analysis in frozen tissue from the middle frontal gyrus revealed decreased levels of the presynaptic protein synaptophysin, but slightly increased levels of the postsynaptic density protein 95 (PSD95) in FTLD-TDP.
- Overall, the proportion of microglia containing synaptic proteins was larger in FTLD-TDP when compared with normal controls.
Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurochemistry international) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2024 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38452814) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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