Neurodegenerative disorders are caused by neuronal cell death, miscommunications between synapse, and abnormal accumulations of proteins in the brain. Alzheimer's disease (AD) is one of the age-related disorders, which are the most common degenerative disorders today, and strongly affects memory consolidation and cognitive function in the brain. Amyloid-β and tau proteins are triggers for AD pathogenesis, and usually used as AD candidate biomarkers in the clinical research. Especially, clinical exam, brain imaging and molecular biological methods are being used to diagnosis for AD. Genome-wide association study (GWAS) is a new biomedical method, and its use contributes to understanding many human diseases, including brain diseases. Here, we identified ubiquitin conjugating enzyme E2 (Ube2) gene expression in neurons through GWAS. The subfamilies of Ube2's genetic expression and inborn errors affect the ubiquitin proteasome system (UPS), leading to protein degradation in the brain. We found that only Ube2h mRNA transcription was significantly increased in the blood from AD, however we did not find any change of Ube2 subfamily genes' expression in the blood and brain tissue. These data may provide information for diagnosis or clinical approach, and suggest that cell-free circulating Ube2h mRNA is a novel potential biomarker for AD.
Keywords: Alzheimer’s disease; E2 ubiquitin conjugating enzyme; Ube2h; ubiquitin.
The Ubiquitin System in Alzheimer's Disease.Adv Exp Med Biol. 2020;1233:195-221. doi: 10.1007/978-3-030-38266-7_8. Adv Exp Med Biol. 2020. PMID: 32274758 Review.
Relationship between amyloid-beta and the ubiquitin-proteasome system in Alzheimer's disease.Neurol Res. 2014 Mar;36(3):276-82. doi: 10.1179/1743132813Y.0000000288. Neurol Res. 2014. PMID: 24512022 Review.
Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer's disease.J Neurovirol. 2019 Oct;25(5):702-709. doi: 10.1007/s13365-018-0695-4. Epub 2019 Jan 4. J Neurovirol. 2019. PMID: 30610738
Mutation screening and association study of the UBE2H gene on chromosome 7q32 in autistic disorder.Psychiatr Genet. 2003 Dec;13(4):221-5. doi: 10.1097/00041444-200312000-00005. Psychiatr Genet. 2003. PMID: 14639049
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease.Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018. Alzheimers Dement. 2018. PMID: 29653606 Free PMC article. Review.
- ICT (20-BR-02-13)/KBRI funded by the Ministry of Science (Korea)
- 2019R1F1A1059595/Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education
- 2017R1D1A1B03030741/Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education