The homeless population experience significant inequalities in health, and there is an increasing appreciation of the potential of lifestyle factors in the development of neurodegenerative diseases, including Parkinson’s disease. We performed a study on the prevalence and distribution of pathological alpha-synuclein deposition throughout the central and peripheral nervous systems in a homeless population.

Forty-four homeless individuals consecutively available for autopsy were recruited. Immunohistochemistry was performed using 5G4 antibody recognizing disease-associated forms of alpha-synuclein, complemented by phospho-synuclein antibody on autopsy tissues collected from 18 regions of the brain and spinal cord, as well as the right and left olfactory bulb, the cauda equina, the extramedullary portion of the vagus nerve, and 27 sites of peripheral organs.

The study cohort consisted of 38 males and 6 females, median age 58 years (range 32–67). Lewy-related pathology was present in the brains of three male cases. One showed Braak stage 2 (60 years old), and two stage 4 (56 and 59 years old). One of the Braak stage 4 cases had Lewy-related pathology in the spinal cord, the cauda equina, and the extramedullary portion of the vagus nerve. Examination of 27 sites of peripheral organs found that all three cases with Lewy-related pathology present in the brain were devoid of peripheral organ alpha-synuclein pathology. Multiple system-type alpha-synuclein pathology was not found.

Our study, representing a snapshot of the homeless population that came to autopsy, suggests that alpha-synuclein pathology is prevalent in the homeless supporting further study of this vulnerable population.

Dementia with Lewy bodies (DLB) is the second most common dementia. Advancing our limited understanding of its molecular pathogenesis is essential for identifying novel biomarkers and therapeutic targets for DLB. DLB is an α-synucleinopathy, and small extracellular vesicles (SEV) from people with DLB can transmit α-synuclein oligomerisation between cells. Post-mortem DLB brains and serum SEV from those with DLB share common miRNA signatures, and their functional implications are uncertain. Hence, we aimed to investigate potential targets of DLB-associated SEV miRNA and to analyse their functional implications.

We identified potential targets of six previously reported differentially expressed miRNA genes in serum SEV of people with DLB (MIR26A1, MIR320C2, MIR320D2, MIR548BA, MIR556, and MIR4722) using miRBase and miRDB databases. We analysed functional implications of these targets using EnrichR gene set enrichment analysis and analysed their protein interactions using Reactome pathway analysis.

These SEV miRNA may regulate 4278 genes that were significantly enriched among the genes involved in neuronal development, cell-to-cell communication, vesicle-mediated transport, apoptosis, regulation of cell cycle, post-translational protein modifications, and autophagy lysosomal pathway, after Benjamini-Hochberg false discovery rate correction at 5%. The miRNA target genes and their protein interactions were significantly associated with several neuropsychiatric disorders and with multiple signal transduction, transcriptional regulation, and cytokine signalling pathways.

Our findings provide in-silico evidence that potential targets of DLB-associated SEV miRNAs may contribute to Lewy pathology by transcriptional regulation. Experimental validation of these dysfunctional pathways is warranted and could lead to novel therapeutic avenues for DLB.

There is no consensus about whether late-onset schizophrenia(LOS) is a type of schizophrenia or a secondary psychotic disorder. One of the theories of the occurrence of late-onset psychoses is neurodegeneration caused by the imbalance of proteostasis.

To study the concentration and expression of alpha-synuclein in patients with LOS compared with controls.

The study involved 42 patients with the ICD-10 criteria of schizophrenia with the onset of the disease after 45 years and 104 controls with no dementia and severe somatic pathology, comparable in age and gender. The alpha-synuclein level was estimated in a lymphocytic cell fraction from patients with LOS N=42 and controls N=104 using the Human alpha-synuclein ELISA kit. The expression of the SNCA gene was studied in 22 LOS patients and 22 controls and determined by PCR using the SYBR Green Supermix kit and the CFX96 instrument in comparison with the referent genes using previously developed primers. LOS group underwent psychopathological examination including scales. Statistics: SPSS 12.0; the Mann–Whitney test; exponential regression analysis; data is given as median (min–max). The level of significance was set at p<0.05.

The alpha-synuclein level is higher in patients with LOS (9.21 (0.78-29.52)) compared to control (6,355 (0.46-35.44)), p=0.024. The mRNA level of the SNCA gene is higher in the LOS group (0.533 (0.089-1.406)) compared to controls (0.087 (0.016-0.266) , p<0.001.

Our study shows the relationship of alpha-synuclein with the manifestations of LOS. Obtained novel data can open up new targets for therapy and bring it closer to understanding the phenomenon.

No significant relationships.