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

• Verfasst von: Stocker, Hannah [VerfasserIn]
• Verfasst von: Gentiluomo, Manuel [VerfasserIn]
• Verfasst von: Trares, Kira [VerfasserIn]
• Verfasst von: Beyer, Léon [VerfasserIn]
• Verfasst von: Stevenson-Hoare, Joshua [VerfasserIn]
• Verfasst von: Rujescu, Dan [VerfasserIn]
• Verfasst von: Holleczek, Bernd [VerfasserIn]
• Verfasst von: Beyreuther, Konrad [VerfasserIn]
• Verfasst von: Gerwert, Klaus [VerfasserIn]
• Verfasst von: Schöttker, Ben [VerfasserIn]
• Verfasst von: Campa, Daniele [VerfasserIn]
• Verfasst von: Canzian, Federico [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Titel: Mitochondrial DNA abundance in blood is associated with Alzheimer’s disease- and dementia-risk
• Verf.angabe: Hannah Stocker, Manuel Gentiluomo, Kira Trares, Léon Beyer, Joshua Stevenson-Hoare, Dan Rujescu, Bernd Holleczek, Konrad Beyreuther, Klaus Gerwert, Ben Schöttker, Daniele Campa, Federico Canzian and Hermann Brenner
• E-Jahr: 2025
• Jahr: January 2025
• Umfang: 9 S.
• Illustrationen: Illustrationen
• Fussnoten: Online veröffentlicht: 15. Juli 2024 ; Gesehen am 27.01.2025
• Titel Quelle: Enthalten in: Molecular psychiatry
• Ort Quelle: [London] : Springer Nature, 1997
• Jahr Quelle: 2025
• Band/Heft Quelle: 30(2025), 1, Seite 131-139
• ISSN Quelle: 1476-5578
• DOI: doi:10.1038/s41380-024-02670-x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Genetics
• Sach-SW: Neuroscience
• Sach-SW: Predictive markers
• K10plus-PPN: 1915636302

Abstract

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.