Please use this identifier to cite or link to this item: https://doi.org/10.1186/s13041-017-0316-9
Title: An iTRAQ-based proteomic analysis reveals dysregulation of neocortical synaptopodin in Lewy body dementias
Authors: Datta, A
Chai, Y.L
Tan, J.M
Lee, J.H 
Francis, P.T
Chen, C.P 
Sze, S.K
Lai, M.K.P 
Keywords: actin binding protein
amyloid beta protein
SYNPO protein, human
demography
diffuse Lewy body disease
female
human
immunoblotting
isotope labeling
male
metabolism
neocortex
pathology
procedures
proteomics
quality control
very elderly
Aged, 80 and over
Amyloid beta-Peptides
Demography
Female
Humans
Immunoblotting
Isotope Labeling
Lewy Body Disease
Male
Microfilament Proteins
Neocortex
Proteomics
Quality Control
Issue Date: 2017
Citation: Datta, A, Chai, Y.L, Tan, J.M, Lee, J.H, Francis, P.T, Chen, C.P, Sze, S.K, Lai, M.K.P (2017). An iTRAQ-based proteomic analysis reveals dysregulation of neocortical synaptopodin in Lewy body dementias. Molecular brain 10 (1) : 36. ScholarBank@NUS Repository. https://doi.org/10.1186/s13041-017-0316-9
Rights: Attribution 4.0 International
Abstract: 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 A?42) 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.
Source Title: Molecular brain
URI: https://scholarbank.nus.edu.sg/handle/10635/179467
ISSN: 17566606
DOI: 10.1186/s13041-017-0316-9
Rights: Attribution 4.0 International
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