Associations of mitochondrial genomic variation with corticobasal degeneration, progressive supranuclear palsy, and neuropathological tau measures

Acta Neuropathologica Communications

卷:8

Zbigniew K. Wszolek¹  Ryan J. Uitti¹  Dennis W. Dickson²  Rebecca R. Valentino²  Owen A. Ross²  Nikoleta Tamvaka²  Alexandra I. Soto-Beasley²  Ronald L. Walton²  Shunsuke Koga²  Patrick W. Johnson³  Michael G. Heckman³ 

[1]Department of Neurology, Mayo Clinic

[2]|Department of Neuroscience, Mayo Clinic

[3]|Division of Biomedical Statistics and Informatics, Mayo Clinic

关键词: Progressive supranuclear palsy;    Corticobasal degeneration;    mtDNA;    Mitochondrial haplogroups;    Tauopathy;    Neuropathology;   

DOI  :  10.1186/s40478-020-01035-z

来源: DOAJ

【 摘 要 】

Abstract Mitochondrial health is important in ageing and dysfunctional oxidative phosphorylation (OXPHOS) accelerates ageing and influences neurodegeneration. Mitochondrial DNA (mtDNA) codes for vital OXPHOS subunits and mtDNA background has been associated with neurodegeneration; however, no study has characterised mtDNA variation in Progressive supranuclear palsy (PSP) or Corticobasal degeneration (CBD) risk or pathogenesis. In this case–control study, 910 (42.6% male) neurologically-healthy controls, 1042 (54.1% male) pathologically-confirmed PSP cases, and 171 (52.0% male) pathologically-confirmed CBD cases were assessed to determine how stable mtDNA polymorphisms, in the form of mtDNA haplogroups, were associated with risk of PSP, risk of CBD, age of PSP onset, PSP disease duration, and neuropathological tau pathology measures for neurofibrillary tangles (NFT), neuropil threads (NT), tufted astrocytes (TA), astrocytic plaques (AP), and oligodendroglial coiled bodies (CB). 764 PSP cases and 150 CBD cases had quantitative tau pathology scores. mtDNA was genotyped for 39 unique SNPs using Agena Bioscience iPlex technologies and mitochondrial haplogroups were defined to mitochondrial phylogeny. After adjustment for multiple testing, we observed an association with risk of CBD for mtDNA sub-haplogroup H4 (OR = 4.51, P = 0.001) and the HV/HV0a haplogroup was associated with a decreased severity of NT tau pathology in PSP cases (P = 0.0023). Our study reports that mitochondrial genomic background may be associated with risk of CBD and may be influencing tau pathology measures in PSP. Replication of these findings will be important.

【 授权许可】

Unknown