Journal
MOLECULAR BRAIN
Volume 9, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13041-016-0205-7
Keywords
Alzheimer's disease; Cerebrovascular disease; Dementia; Temporal lobe; White matter; Citrullination; Deamidation; Proteomics; iTRAQ
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Funding
- Singapore Ministry of Health [NMRC/CBRG/0004/2012]
- Singapore Ministry of Education [RGT15/13]
- NTU-NHG Ageing Research Grant [ARG/14017]
- PHS [HHSN-271-2013-00030C]
- Medical Research Council [G0502157, G0400074, G1100540, G0900652] Funding Source: researchfish
- MRC [G0900652, G0502157, G0400074, G1100540] Funding Source: UKRI
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Background: Dementia risk in women is higher than in men, but the molecular neuropathology of this gender difference remains poorly defined. In this study, we used unbiased, discovery-driven quantitative proteomics to assess the molecular basis of gender influences on risk of Alzheimer's disease with cerebrovascular disease (AD + CVD). Results: We detected modulation of several redox proteins in the temporal lobe of AD + CVD subjects, and we observed sex-specific alterations in the white matter (WM) and mitochondria proteomes of female patients. Functional proteomic analysis of AD + CVD brain tissues revealed increased citrullination of arginine and deamidation of glutamine residues of myelin basic protein (MBP) in female which impaired degradation of degenerated MBP and resulted in accumulation of non-functional MBP in WM. Female patients also displayed down-regulation of ATP sub-units and cytochromes, suggesting increased severity of mitochondria impairment in women. Conclusions: Our study demonstrates that gender-linked modulation of white matter and mitochondria proteomes influences neuropathology of the temporal lobe in AD + CVD.
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