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α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies
Frederique J Hart de Ruyter, Tjado H J Morrema, Jurre den Haan, Gina Gase, Jos W R Twisk, Johannes F de Boer, Philip Scheltens, Femke H Bouwman et al.. NPJ Parkinson's disease, 2023-08-28
Topic: Disease mechanisms in lab and animal studies
There is increasing interest in studying retinal biomarkers for various neurodegenerative diseases. Specific protein aggregates associated with neurodegenerative diseases are present in the retina and could be visualised in a non-invasive way. This study aims to assess the specificity and sensitivity of retinal α-synuclein aggregates in neuropathologically characterised α-synucleinopathies, other neurodegenerative diseases and non-neurological controls. Post-mortem eyes (N = 99) were collected prospectively through the Netherlands Brain Bank from donors with Parkinson's disease (and dementia), dementia with Lewy bodies, multiple system atrophy, Alzheimer's disease, other neurodegenerative diseases and non-neurological controls. Multiple retinal and optic nerve cross-sections were immunostained with anti-α-synuclein antibodies (LB509, KM51, and anti-pSer129) and assessed for aggregates and inclusions. α-Synuclein was observed as Lewy neurites in the retina and oligodendroglial cytoplasmic inclusions in the optic nerve and was highly associated with Lewy body disease (P < 0.001) and multiple system atrophy (P = 0.001). In all multiple system atrophy cases, the optic nerve showed oligodendroglial cytoplasmic inclusions, while retinal Lewy neurites were absent, despite coincidental brain Lewy pathology. With high specificity (97%) and sensitivity (82%), retinal/optic nerve α-synuclein differentiates primary α-synucleinopathies from other cases and controls. α-Synuclein pathology occurs specifically in the retina and optic nerve of primary α-synucleinopathies as opposed to other neurodegenerative diseases-with and without α-synuclein co-pathology-and controls. The absence of retinal Lewy neurites in multiple system atrophy could contribute to the development of an in vivo retinal biomarker that discriminates between Lewy body disease and multiple system atrophy.
Key findings
- Specific protein aggregates associated with neurodegenerative diseases are present in the retina and could be visualised in a non-invasive way.
- Multiple retinal and optic nerve cross-sections were immunostained with anti-α-synuclein antibodies (LB509, KM51, and anti-pSer129) and assessed for aggregates and inclusions. α-Synuclein was observed as Lewy neurites in the retina and oligodendroglial cytoplasmic inclusions in the optic nerve and was highly associated with Lewy body disease (P < 0.001) and multiple system atrophy (P = 0.001).
Study details
- Participants99
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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, multi-centre collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NPJ Parkinson's disease) |
| 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 | 3 / 5 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 99 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 37640753) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
de Ruyter, F. J. H., Morrema, T. H. J., den Haan, J., Gase, G., Twisk, J. W. R., de Boer, J. F., et al. (2023). α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies. NPJ Parkinson's disease. https://doi.org/10.1038/s41531-023-00570-5
Vancouver
de Ruyter FJH, Morrema THJ, den Haan J, Gase G, Twisk JWR, de Boer JF, et al. α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies. NPJ Parkinson's disease. 2023. doi:10.1038/s41531-023-00570-5. PMID: 37640753.
BibTeX
@article{deruyter2023-37640753,
author = {de Ruyter, Frederique J Hart and Morrema, Tjado H J and den Haan, Jurre and Gase, Gina and Twisk, Jos W R and de Boer, Johannes F and Scheltens, Philip and Bouwman, Femke H and others},
title = {{α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies}},
journal = {NPJ Parkinson's disease},
year = {2023},
doi = {10.1038/s41531-023-00570-5},
pmid = {37640753},
url = {https://doi.org/10.1038/s41531-023-00570-5}
}
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