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@ARTICLE{Stocker:291769,
      author       = {H. Stocker$^*$ and M. Gentiluomo and K. Trares$^*$ and L.
                      Beyer and J. Stevenson-Hoare$^*$ and D. Rujescu and B.
                      Holleczek and K. Beyreuther and K. Gerwert and B.
                      Schöttker$^*$ and D. Campa and F. Canzian$^*$ and H.
                      Brenner$^*$},
      title        = {{M}itochondrial {DNA} abundance in blood is associated with
                      {A}lzheimer's disease- and dementia-risk.},
      journal      = {Molecular psychiatry},
      volume       = {30},
      issn         = {1359-4184},
      address      = {London},
      publisher    = {Macmillan},
      reportid     = {DKFZ-2024-01505},
      pages        = {131–139},
      year         = {2025},
      note         = {#EA:C070#LA:C070# / 30, pages 131–139 (2025)},
      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.},
      cin          = {C070 / C055},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C055-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39009700},
      doi          = {10.1038/s41380-024-02670-x},
      url          = {https://inrepo02.dkfz.de/record/291769},
}