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@ARTICLE{Stocker:300574,
      author       = {H. Stocker$^*$ and L. Beyer and K. Trares$^*$ and J.
                      Stevenson-Hoare$^*$ and D. Rujescu and B. Holleczek and K.
                      Beyreuther and B. Schöttker$^*$ and K. Gerwert and H.
                      Brenner$^*$},
      title        = {{A}ssociation of {N}onmodifiable {R}isk {F}actors {W}ith
                      {A}lzheimer {D}isease {B}lood {B}iomarkers in
                      {C}ommunity-{D}welling {A}dults in the {ESTHER} {S}tudy.},
      journal      = {Neurology},
      volume       = {104},
      number       = {9},
      issn         = {0028-3878},
      address      = {Philadelphia, Pa.},
      publisher    = {Wolters Kluwer},
      reportid     = {DKFZ-2025-00807},
      pages        = {e213500},
      year         = {2025},
      note         = {#EA:C070#LA:C070#},
      abstract     = {Dementia-related blood biomarkers are the future of
                      large-scale dementia risk stratification; however, the
                      extent to which phosphorylated tau (P-tau181), neurofilament
                      light (NfL), and glial fibrillary acidic protein (GFAP) are
                      associated with nonmodifiable risk factors has yet to be
                      confirmed in the community, and the role of menopause has
                      yet to be investigated. Therefore, the aim of this study was
                      to examine the association of age, sex, APOEe4 status, and
                      menopause, with dementia-related blood biomarker levels
                      (P-tau181, NfL, and GFAP) and rate of change over 11 years
                      in longitudinal biomarker measurements in community-dwelling
                      adults.Within this German population-based Epidemiologische
                      Studie zu Chancen der Verhütung, Früherkennung und
                      optimierten Therapie chronischer Erkrankungen in der
                      älteren Bevölkerung cohort study (n = 9,940), a nested
                      case-control study of 1,026 participants (1:1, without
                      dementia during follow-up: incident dementia during
                      follow-up) aged 50-75 years at baseline followed over 17
                      years was conducted. Blood biomarker measurements (P-tau181,
                      NfL, and GFAP) were completed in blood from baseline,
                      8-year, and 11-year follow-ups, and cross-sectional and
                      longitudinal regression analyses were used to assess the
                      association with age, sex, APOEe4, and menopause.The mean
                      age of participants was 64 years, and women accounted for
                      slightly over half $(54\%)$ of the sample. Age was
                      cross-sectionally and longitudinally significantly
                      associated with all dementia-related biomarkers (p < 0.001).
                      NfL and GFAP levels more strongly correlated (Spearman R =
                      0.55 and 0.49) with age at baseline than P-tau181 levels
                      (Spearman R = 0.21). Women experienced significantly higher
                      levels and rates of increase in GFAP (p < 0.001) while men
                      experienced higher levels of NfL after adjusting for age and
                      APOEe4 (p < 0.01). APOEe4 status was significantly
                      associated with baseline and longitudinal levels of P-tau181
                      (baseline β = 0.30, p < 0.05) and GFAP (baseline β =
                      15.84, p < 0.001). Of interest, premenopausal status was
                      significantly associated with higher GFAP levels after
                      adjusting for age, sex, and APOEe4 (β = 19.09, p <
                      0.05).This population-based study on dementia biomarkers
                      found that P-tau181 was dependent on age and APOEe4; NfL on
                      age and sex; and GFAP on age, sex, APOEe4, and menopause
                      status. GFAP levels and rate of increase were higher in
                      women, especially in premenopausal participants. Future
                      research should confirm these findings and further explore
                      the role of menopause in dementia pathogenesis among women.},
      keywords     = {Humans / Female / Male / Biomarkers: blood / Aged / Middle
                      Aged / Alzheimer Disease: blood / Alzheimer Disease:
                      epidemiology / Alzheimer Disease: genetics / tau Proteins:
                      blood / Neurofilament Proteins: blood / Risk Factors / Glial
                      Fibrillary Acidic Protein: blood / Longitudinal Studies /
                      Case-Control Studies / Independent Living / Germany:
                      epidemiology / Menopause: blood / Cohort Studies /
                      Apolipoprotein E4: genetics / Age Factors / Sex Factors /
                      Biomarkers (NLM Chemicals) / tau Proteins (NLM Chemicals) /
                      Neurofilament Proteins (NLM Chemicals) / neurofilament
                      protein L (NLM Chemicals) / Glial Fibrillary Acidic Protein
                      (NLM Chemicals) / GFAP protein, human (NLM Chemicals) /
                      Apolipoprotein E4 (NLM Chemicals)},
      cin          = {C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40239154},
      doi          = {10.1212/WNL.0000000000213500},
      url          = {https://inrepo02.dkfz.de/record/300574},
}