Neuropathological hallmarks in the post-mortem retina of neurodegenerative diseases.

Autor: Hart de Ruyter FJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. f.hartderuijter@amsterdamumc.nl.; Amsterdam UMC, Vrije Universiteit Amsterdam, Alzheimer Center Amsterdam, Neurology, De Boelelaan 1117, Amsterdam, The Netherlands. f.hartderuijter@amsterdamumc.nl., Evers MJAP; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Morrema THJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Dijkstra AA; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., den Haan J; Amsterdam UMC, Vrije Universiteit Amsterdam, Alzheimer Center Amsterdam, Neurology, De Boelelaan 1117, Amsterdam, The Netherlands., Twisk JWR; Epidemiology and Data Science, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, The Netherlands., de Boer JF; LaserLaB, Physics and Astronomy, Vrije Universiteit Amsterdam, De Boelelaan 1081, Amsterdam, The Netherlands., Scheltens P; Amsterdam UMC, Vrije Universiteit Amsterdam, Alzheimer Center Amsterdam, Neurology, De Boelelaan 1117, Amsterdam, The Netherlands., Bouwman FH; Amsterdam UMC, Vrije Universiteit Amsterdam, Alzheimer Center Amsterdam, Neurology, De Boelelaan 1117, Amsterdam, The Netherlands., Verbraak FD; Amsterdam UMC, Vrije Universiteit Amsterdam, Ophthalmology, De Boelelaan 1117, Amsterdam, The Netherlands., Rozemuller AJ; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. jm.rozemuller@amsterdamumc.nl., Hoozemans JJM; Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Acta neuropathologica [Acta Neuropathol] 2024 Aug 19; Vol. 148 (1), pp. 24. Date of Electronic Publication: 2024 Aug 19.
DOI: 10.1007/s00401-024-02769-z
Abstrakt: The retina is increasingly recognised as a potential source of biomarkers for neurodegenerative diseases. Hallmark protein aggregates in the retinal neuronal tissue could be imaged through light non-invasively. Post-mortem studies have already shown the presence of specific hallmark proteins in Alzheimer's disease, primary tauopathies, synucleinopathies and frontotemporal lobar degeneration. This study aims to assess proteinopathy in a post-mortem cohort with different neurodegenerative diseases and assess the presence of the primary pathology in the retina. Post-mortem eyes were collected in collaboration with the Netherlands Brain Bank from donors with Alzheimer's disease (n = 17), primary tauopathies (n = 8), synucleinopathies (n = 27), frontotemporal lobar degeneration (n = 8), mixed pathology (n = 11), other neurodegenerative diseases (n = 6), and cognitively normal controls (n = 25). Multiple cross sections of the retina and optic nerve tissue were immunostained using antibodies against pTau Ser202/Thr205 (AT8), amyloid-beta (4G8), alpha-synuclein (LB509), pTDP-43 Ser409/410 and p62-lck ligand (p62) and were assessed for the presence of aggregates and inclusions. pTau pathology was observed as a diffuse signal in Alzheimer's disease, primary tauopathies and controls with Alzheimer's disease neuropathological changes. Amyloid-beta was observed in the vessel wall and as cytoplasmic granular deposits in all groups. Alpha-synuclein pathology was observed as Lewy neurites in the retina in synucleinopathies associated with Lewy pathology and as oligodendroglial cytoplasmic inclusions in the optic nerve in multiple system atrophy. Anti-pTDP-43 generally showed typical neuronal cytoplasmic inclusion bodies in cases with frontotemporal lobar degeneration with TDP-43 and also in cases with later stages of limbic-associated TDP-43 encephalopathy. P62 showed inclusion bodies similar to those seen with anti-pTDP-43. Furthermore, pTau and alpha-synuclein pathology were significantly associated with increasing Braak stages for neurofibrillary tangles and Lewy bodies, respectively. Mixed pathology cases in this cohort consisted of cases (n = 6) with high Braak LB stages (> 4) and low or moderate AD pathology, high AD pathology (n = 1, Braak NFT 6, Thal phase 5) with moderate LB pathology, or a combination of low/moderate scores for different pathology scores in the brain (n = 4). There were no cases with advanced co-pathologies. In seven cases with Braak LB ≥ 4, LB pathology was observed in the retina, while tau pathology in the retina in the mixed pathology group (n = 11) could not be observed. From this study, we conclude that the retina reflects the presence of the major hallmark proteins associated with neurodegenerative diseases. Although low or moderate levels of copathology were found in the brains of most cases, the retina primarily manifested protein aggregates associated with the main neurodegenerative disease. These findings indicate that with appropriate retinal imaging techniques, retinal biomarkers have the potential to become highly accurate indicators for diagnosing the major neurodegenerative diseases of the brain.
(© 2024. The Author(s).)
Databáze: MEDLINE
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