α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies
Abstract 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 s...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00570-5 |
| _version_ | 1827723944681013248 |
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| author | 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 Frank D. Verbraak Annemieke J. M. Rozemuller Jeroen J. M. Hoozemans |
| author_facet | 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 Frank D. Verbraak Annemieke J. M. Rozemuller Jeroen J. M. Hoozemans |
| author_sort | Frederique J. Hart de Ruyter |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T22:07:56Z |
| format | Article |
| id | doaj.art-f133d6ba3b3b465b90db3046c23ce62f |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-10T22:07:56Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-f133d6ba3b3b465b90db3046c23ce62f2023-11-19T12:45:49ZengNature Portfolionpj Parkinson's Disease2373-80572023-08-01911910.1038/s41531-023-00570-5α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathiesFrederique J. Hart de Ruyter0Tjado H. J. Morrema1Jurre den Haan2Gina Gase3Jos W. R. Twisk4Johannes F. de Boer5Philip Scheltens6Femke H. Bouwman7Frank D. Verbraak8Annemieke J. M. Rozemuller9Jeroen J. M. Hoozemans10Department of Pathology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Pathology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Pathology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Epidemiology and Data Science, Vrije Universiteit AmsterdamDepartment of Physics and Astronomy and LaserLaB, Vrije Universiteit AmsterdamDepartment of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Neurology and Alzheimer Center Amsterdam, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Ophthalmology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Pathology, Amsterdam UMC location Vrije Universiteit AmsterdamDepartment of Pathology, Amsterdam UMC location Vrije Universiteit AmsterdamAbstract 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.https://doi.org/10.1038/s41531-023-00570-5 |
| spellingShingle | 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 Frank D. Verbraak Annemieke J. M. Rozemuller Jeroen J. M. Hoozemans α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies npj Parkinson's Disease |
| title | α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies |
| title_full | α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies |
| title_fullStr | α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies |
| title_full_unstemmed | α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies |
| title_short | α-Synuclein pathology in post-mortem retina and optic nerve is specific for α-synucleinopathies |
| title_sort | α synuclein pathology in post mortem retina and optic nerve is specific for α synucleinopathies |
| url | https://doi.org/10.1038/s41531-023-00570-5 |
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