Gender differences in white matter pathology and mitochondrial dysfunction in Alzheimer’s disease with cerebrovascular disease

Autor: Jingru Qian, Aida Serra, Christopher Chen, Xavier Gallart-Palau, Siu Kwan Sze, Benjamin Sian Teck Lee, Raj N. Kalaria, Sunil S. Adav, Mitchell K.P. Lai, Jung Eun Park
Přispěvatelé: School of Biological Sciences
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Proteomics
Male
Pathology
Proteome
Mitochondrion
0302 clinical medicine
Medicine
Amino Acids
Cerebrovascular disease
Aged
80 and over
Sex Characteristics
biology
White matter
Citrullination
Temporal Lobe
Science::Biological sciences [DRNTU]
Mitochondria
medicine.anatomical_structure
Female
Alzheimer's disease
Alzheimer’s disease
medicine.medical_specialty
Neuropathology
Temporal lobe
03 medical and health sciences
Cellular and Molecular Neuroscience
Alzheimer Disease
Internal medicine
Dementia
Humans
Alzheimer’s Disease
Molecular Biology
Aged
Demography
business.industry
Research
Myelin Basic Protein
medicine.disease
Myelin basic protein
Cerebrovascular Disorders
030104 developmental biology
Endocrinology
iTRAQ
Cerebrovascular Disease
Case-Control Studies
Nerve Degeneration
biology.protein
Deamidation
business
030217 neurology & neurosurgery
Zdroj: Molecular Brain
ISSN: 1756-6606
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1186/s13041-016-0205-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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