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000291769 1001_ $$0P:(DE-He78)104fae0755c89365b7ae32238b3f1f52$$aStocker, Hannah$$b0$$eFirst author$$udkfz
000291769 245__ $$aMitochondrial DNA abundance in blood is associated with Alzheimer's disease- and dementia-risk.
000291769 260__ $$aLondon$$bMacmillan$$c2025
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000291769 520__ $$aThe 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.
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000291769 7001_ $$aGentiluomo, Manuel$$b1
000291769 7001_ $$0P:(DE-He78)b09508a4c4afe85c57dd131eefa689ea$$aTrares, Kira$$b2$$udkfz
000291769 7001_ $$aBeyer, Léon$$b3
000291769 7001_ $$0P:(DE-He78)9976da2c4ac21202b44584c21d8404e7$$aStevenson-Hoare, Joshua$$b4$$udkfz
000291769 7001_ $$00000-0002-1432-313X$$aRujescu, Dan$$b5
000291769 7001_ $$aHolleczek, Bernd$$b6
000291769 7001_ $$aBeyreuther, Konrad$$b7
000291769 7001_ $$aGerwert, Klaus$$b8
000291769 7001_ $$0P:(DE-He78)c67a12496b8aac150c0eef888d808d46$$aSchöttker, Ben$$b9$$udkfz
000291769 7001_ $$aCampa, Daniele$$b10
000291769 7001_ $$0P:(DE-He78)5323704270b6393dcea70186ffd86bca$$aCanzian, Federico$$b11$$udkfz
000291769 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b12$$eLast author$$udkfz
000291769 773__ $$0PERI:(DE-600)1502531-7$$a10.1038/s41380-024-02670-x$$p131–139$$tMolecular psychiatry$$v30$$x1359-4184$$y2025
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