Lewy body
dementias are the second most common cause of neurodegenerative
dementia in the elderly after
Alzheimer's disease (AD). The two clinical subgroups of Lewy body
dementias, namely,
dementia with Lewy bodies (DLB) and
Parkinson's disease dementia (PDD), are differentiated by the chronology of
cognitive symptoms relative to
parkinsonism. At present, there remains a debate on whether DLB and PDD are separate disease entities, or fall within the same spectrum of Lewy body
dementias. In this study, we compared the
detergent-soluble
proteome via an 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) analysis of pooled lysates from the prefrontal cortex (BA9) of DLB (n = 19) and PDD (n = 21) patients matched a priori for
amyloid (total Aβ42) burden, semi-quantitative scores for Lewy bodies and neurofibrillary tangles together with age-matched control (n = 21) subjects. A total of 1914
proteins were confidently identified by iTRAQ (false discovery rate = 0%). None of the
proteins showed a significant yet opposite regulation in between DLB and PDD when compared to aged controls in the proteomic data set as well as following immunoblot analysis of the pooled and individual lysates involving all 61 subjects. The postsynaptic
protein, synaptopodin (SYNPO) was significantly down-regulated in both DLB and PDD subgroups, suggesting a defective synaptic transmission in the demented patients. In conclusion, the largely similar
proteome of DLB and PDD matched for
amyloid burden suggests that variations in concomitant AD-related pathology, abnormal post-translational modifications or
protein-
protein interactions, defective intracellular trafficking or misfolding of
proteins could play a part in driving the clinically observed differences between these two subgroups of Lewy body
dementias. This further indicates that
amyloid-targeting therapeutic strategies may show different efficacies in DLB versus PDD.