Mitochondrial DNA abundance in blood is associated with Alzheimer's disease- and dementia-risk.

Autor: Stocker H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. h.stocker@dkfz-heidelberg.de.; Network Aging Research, Heidelberg University, Heidelberg, Germany. h.stocker@dkfz-heidelberg.de., Gentiluomo M; Department of Biology, University of Pisa, Pisa, Italy., Trares K; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany., Beyer L; Center for Protein Diagnostics (ProDi), Ruhr-University Bochum, Bochum, Germany.; Faculty of Biology and Biotechnology, Department of Biophysics, Ruhr-University Bochum, Bochum, Germany., Stevenson-Hoare J; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany., Rujescu D; Department of Psychiatry, Medical University of Vienna, Vienna, Austria., Holleczek B; Saarland Cancer Registry, Saarbrücken, Germany., Beyreuther K; Network Aging Research, Heidelberg University, Heidelberg, Germany., Gerwert K; Center for Protein Diagnostics (ProDi), Ruhr-University Bochum, Bochum, Germany.; Faculty of Biology and Biotechnology, Department of Biophysics, Ruhr-University Bochum, Bochum, Germany., Schöttker B; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany., Campa D; Department of Biology, University of Pisa, Pisa, Italy., Canzian F; Genomic Epidemiology, German Cancer Research Center, Heidelberg, Germany., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2025 Jan; Vol. 30 (1), pp. 131-139. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1038/s41380-024-02670-x
Abstrakt: The mitochondrial cascade hypothesis of Alzheimer's disease (AD) has been portrayed through molecular, cellular, and animal studies; however large epidemiological studies are lacking. This study aimed to explore the association of mitochondrial DNA copy number (mtDNAcn), a marker representative of mtDNA abundance per cell, with risk of incident all-cause dementia, AD, and vascular dementia diagnosis within 17 years and dementia-related blood biomarkers (P-tau181, GFAP, and NfL). Additionally, sex-stratified analyses were completed. In this German population-based cohort study (ESTHER), 9940 participants aged 50-75 years were enrolled by general practitioners and followed for 17 years. Participants were included in this study if information on dementia status and blood-based mtDNAcn measured via real-time polymerase chain reaction were available. In a nested case-control approach, a subsample of participants additionally had measurements of P-tau181, GFAP, and NfL in blood samples taken at baseline. Of 4913 participants eligible for analyses, 386 were diagnosed with incident all-cause dementia, including 130 AD and 143 vascular dementia cases, while 4527 participants remained without dementia diagnosis within 17 years. Participants with low mtDNAcn (lowest 10%) experienced 45% and 65% percent increased risk of incident all-cause dementia and AD after adjusting for age and sex (all-cause dementia: HRadj, 95%CI:1.45, 1.08-1.94; AD: HRadj, 95%CI: 1.65, 1.01-2.68). MtDNAcn was not associated to vascular dementia diagnosis and was more strongly associated with all-cause dementia among women. In the nested case-control study (n = 790), mtDNAcn was not significantly associated with the dementia-related blood biomarkers (P-tau181, GFAP, and NfL) levels in blood from baseline before dementia diagnosis. This study provides novel epidemiological evidence connecting mtDNA abundance, measured via mtDNAcn, to incident dementia and AD at the population-based level. Reduced mitochondrial abundance may play a role in pathogenesis, especially among women.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: