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Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies
Sengupta U, Guerrero-Muñoz MJ, Castillo-Carranza DL, Lasagna-Reeves CA, Gerson JE, Paulucci-Holthauzen AA, Krishnamurthy S, Farhed M et al.. Biological psychiatry, 2015-01-09
Topic: Disease mechanisms in lab and animal studies
Background Aberrant accumulation of α-synuclein constitutes inclusion bodies that are considered a characteristic feature of a group of neurological disorders described as synucleinopathies. Often, multiple disease-causing proteins overlap within a given disease pathology. An emerging body of research focuses on the oligomeric populations of various pathogenic proteins, considering them as the culprits causing neuronal damage and degeneration. To this end, the use of conformation-specific antibodies has proven to be an effective tool. Previous work from our laboratory and others has shown that oligomeric entities of α-synuclein and tau accumulate in their respective diseases, but their interrelationship at this higher order has yet to be shown in synucleinopathies. Methods Here, we used two novel conformation-specific antibodies, F8H7 and Syn33, which recognize α-synuclein oligomers and were developed in our laboratory. We investigated brain tissue from five of each Parkinson's disease and dementia with Lewy bodies patients by performing biophysical and biochemical assays using these antibodies, in addition to the previously characterized anti-tau oligomer antibody T22. Results We demonstrate that in addition to the deposition of oligomeric α-synuclein, tau oligomers accumulate in these diseased brains compared with control brains. Moreover, we observed that oligomers of tau and α-synuclein exist in the same aggregates, forming hybrid oligomers in these patients' brains. Conclusions In addition to the deposition of tau oligomers, our results also provide compelling evidence of co-occurrence of α-synuclein and tau into their most toxic forms, i.e., oligomers suggesting that these species interact and influence each other's aggregation via an interface in synucleinopathies.
Key findings
- Previous work from our laboratory and others has shown that oligomeric entities of α-synuclein and tau accumulate in their respective diseases, but their interrelationship at this higher order has yet to be shown in synucleinopathies.
- Results We demonstrate that in addition to the deposition of oligomeric α-synuclein, tau oligomers accumulate in these diseased brains compared with control brains.
- Moreover, we observed that oligomers of tau and α-synuclein exist in the same aggregates, forming hybrid oligomers in these patients' brains.
- Conclusions In addition to the deposition of tau oligomers, our results also provide compelling evidence of co-occurrence of α-synuclein and tau into their most toxic forms, i.e., oligomers suggesting that these species interact and influence each other's aggregation via an interface in synucleinopathies.
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Study details
- Evidence strengthLow
How this study scored 36/100
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. 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 and multi-centre collaboration, so those were left out: it earned 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biological psychiatry) |
| 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 | 1 / 5 | 2015 — within 20 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25676491) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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APA 7th
Sengupta, U., Guerrero-Muñoz, M. J., Castillo-Carranza, D. L., Lasagna-Reeves, C. A., Gerson, J. E., Paulucci-Holthauzen, A. A., et al. (2015). Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies. Biological psychiatry. https://doi.org/10.1016/j.biopsych.2014.12.019
Vancouver
Sengupta U, Guerrero-Muñoz MJ, Castillo-Carranza DL, Lasagna-Reeves CA, Gerson JE, Paulucci-Holthauzen AA, et al. Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies. Biological psychiatry. 2015. doi:10.1016/j.biopsych.2014.12.019. PMID: 25676491.
BibTeX
@article{sengupta2015-25676491,
author = {Sengupta, U. and Guerrero-Muñoz, M. J. and Castillo-Carranza, D. L. and Lasagna-Reeves, C. A. and Gerson, J. E. and Paulucci-Holthauzen, A. A. and Krishnamurthy, S. and Farhed, M. and others},
title = {{Pathological interface between oligomeric alpha-synuclein and tau in synucleinopathies}},
journal = {Biological psychiatry},
year = {2015},
doi = {10.1016/j.biopsych.2014.12.019},
pmid = {25676491},
url = {https://doi.org/10.1016/j.biopsych.2014.12.019}
}