- Authors: Evans, T., Kok, W. L., Cowan, K., Hefford, M., Anichtchik, O.
- Year: 2018
- Journal: Brain Res 1681 1-13
- Applications: in vitro / DNA / jetPRIME
- Cell types:
- Name: BE(2)-M17
Description: Human bone marrow neuroblastoma
- Name: HeLa
Description: Human cervix epitheloid carcinoma cells
- Name: BE(2)-M17
Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls. We provide evidence for neuronal upregulation of beta-synuclein within the frontal cortex and its decrease in occipital cortex of DLB patients. While beta-synuclein-containing neurons were consistently devoid of oligomeric alpha-synuclein in the frontal cortex, we did not observe an overall correlation between total beta-synuclein and 5G4 levels (marker of oligomeric alpha-synuclein). The autophagy markers LC3-II and p62 were increased in the areas of beta-synuclein upregulation in DLB brains, and we show attenuation of autophagy flux when beta-synuclein is overexpressed in vitro. Altogether, this data suggests that beta-synuclein changes in DLB may exacerbate neuronal dysfunction caused by accumulation of alpha-synuclein by influencing protein degradation pathways; this should be taken into consideration when designing therapeutic strategies aimed to decrease alpha-synuclein burden in Lewy body diseases.