Accumulation of Insoluble α-Synuclein in Dementia with Lewy Bodies (original) (raw)

2000, Neurobiology of Disease

The ␣-synuclein (␣SN) protein is thought to play a central role in the pathogenesis of neurodegenerative diseases where it aggregates to form intracellular inclusions. We have used Western blotting to examine the expression levels and solubility of ␣SN in brain homogenates from dementia with Lewy bodies (DLB), Parkinson's disease (PD), Alzheimer's disease (AD), and normal controls using samples from the parahippocampus/transentorhinal cortex. Compared to controls, DLB brains accumulate significantly greater amounts of sodium dodecyl sulfate (SDS)-soluble and SDS-insoluble ␣SN but levels of TBS-soluble ␣SN did not change. Levels of synaptophysin, a marker of synaptic integrity, were significantly lower in DLB cases than in normal aged controls regardless of whether concurrent changes of AD were present. This limbic synaptic dysfunction may contribute to cognitive impairment in DLB. Whether aggregated ␣SN is a cause or effect of the disease process in DLB and PD remains to be determined, but the presence of aggregated ␣SN is consistent with a pathogenesis similar to that associated with aggregates of A␤ amyloid in AD.

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