Objective: To study the prevalence and distribution of pathological alpha-synuclein deposition, throughout the central and peripheral nervous systems, in a homeless population.

Background: The homeless experience significant inequalities in health, including a shorter life expectancy and increased morbidity. There is an increasing appreciation of the potential role for a wide range of lifestyle factors in the development of neurodegenerative diseases, including Parkinson’s disease. Here we performed a study on the presence of Parkinson’s disease associated alpha-synuclein pathology in a homeless population.

Method: 43 consecutive individuals available for autopsy, who met the study inclusion criteria of being homeless, were recruited between November 2017 and February 2018 at the Department of Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary. Autopsy tissues were collected from 24 brain regions and 30 peripheral sites. Immunohistochemistry was performed using 5G4, an antibody which selectively recognises disease associated forms of alpha-synuclein 1.

Results: The study cohort consisted of 38 males and 5 females, median age 58 years (range 32-67), with a median postmortem delay of 4 days (range 0-14). Lewy-related pathology was present in the brains of a total of 3 male cases. Two of them showed Braak stage 2 (59 and 60 years-old) and one stage 4 (62 years-old).  Further examination of 30 peripheral sites from these 3 cases found the two Braak stage 2 cases to be devoid of peripheral alpha-synuclein pathology, whilst the single Braak stage 4 case had evidence of abnormal alpha-synuclein deposition in the spinal cord, cauda equina and medullary vagus nerve, but no nerve-associated deposits were seen in peripheral organs. All 3 cases, as well as an additional 5 cases which did not show cerebral Lewy-related pathology, had evidence of 5G4 positive tissue macrophages.

Conclusion: To our knowledge this is the first study of the presence and distribution of alpha-synuclein pathology in a homeless cohort. Our findings suggest that pathological deposition of alpha-synuclein is prevalent in the homeless and supports the further study of this vulnerable population.

References: 1. An antibody with high reactivity for disease-associated α-synuclein reveals extensive brain pathology. Kovacs GG, Wagner U, Dumont B, Pikkarainen M, Osman AA, Streichenberger N, Leisser I, Verchère J, Baron T, Alafuzoff I, Budka H, Perret-Liaudet A, Lachmann I. Acta Neuropathol. 2012 Jul;124(1):37-50. doi: 10.1007/s00401-012-0964-x. Epub 2012 Feb 28.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-and-distribution-of-disease-associated-alpha-synuclein-in-a-homeless-population/