The protein alpha-synuclein (ASYN) is thought to be involved in the development 
of dementia with Lewy bodies (DLB). Overexpression of ASYN has been linked to 
cellular toxicity and human disease, and in experimental models, chaperones such 
as heat shock proteins (HSPs) are protective against ASYN toxicity. We have 
assessed the abundance of mRNA for ASYN and chaperones and the abundance and 
solubility of the encoded proteins in temporal cortex from sporadic human DLB. 
We found a reduction of ASYN mRNA in DLB (44.9% of control). The abundance of 
the Triton-soluble fraction (bioavailable protein) was not altered, but there 
was an increase of the Triton-insoluble component (likely representing 
aggregates). We evaluated 3 chaperones: HSP70, HSP90, and HDJ1. HSP70 mRNA was 
increased in DLB, whereas the mRNAs for HSP90 and HDJ1 were unchanged. HSP70 
accumulated in the Triton-soluble fraction, whereas HSP90 and HDJ1 proteins 
accumulated in the Triton-insoluble fraction. These observations suggest that 
sporadic DLB is not associated with overexpression of ASYN. Rather, the 
persistence of normal soluble ASYN protein levels, despite the reduction of its 
mRNA, suggests a primary defect in clearance of the protein. However, this 
reduced clearance cannot be attributed to a failure of chaperone expression, 
because their mRNA is unchanged or increased in the DLB brain.