title: Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer's disease with cerebrovascular disease.
abstract: 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.
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gallart-Palau
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Benjamin S T
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Sunil S
authors.initials: SS
authors.lastname: Adav
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Jingru
authors.initials: J
authors.lastname: Qian
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Aida
authors.initials: A
authors.lastname: Serra
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Memory, Aging and Cognition Centre, National University Health System, Singapore, Singapore.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Institute for Ageing and Health, NIHR Biomedical Research Building, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.
authors.forename: Raj N
authors.initials: RN
authors.lastname: Kalaria
authors.affiliation: Division of Chemical Biology & BioTechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore. sksze@ntu.edu.sg.
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D000596:Amino Acids / Q000378:metabolism; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000473:pathology*; D003710:Demography; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D012727:Sex Characteristics; D013702:Temporal Lobe / Q000378:metabolism; D066127:White Matter / Q000473:pathology*
chemical_list: D000596:Amino Acids; D004676:Myelin Basic Protein; D020543:Proteome
keywords: Alzheimer’s disease; Cerebrovascular disease; Citrullination; Deamidation; Dementia; Proteomics; Temporal lobe; White matter; iTRAQ