% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Stocker:277864,
      author       = {H. Stocker$^*$ and K. Trares$^*$ and L. Beyer and L. Perna
                      and D. Rujescu and B. Holleczek and K. Beyreuther and K.
                      Gerwert and B. Schöttker$^*$ and H. Brenner$^*$},
      title        = {{A}lzheimer's polygenic risk scores, {APOE}, {A}lzheimer's
                      disease risk, and dementia-related blood biomarker levels in
                      a population-based cohort study followed over 17 years.},
      journal      = {Alzheimer's research $\&$ therapy},
      volume       = {15},
      number       = {1},
      issn         = {1758-9193},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-01532},
      pages        = {129},
      year         = {2023},
      note         = {#EA:C070#LA:C070#},
      abstract     = {In order to utilize polygenic risk scores (PRSs) for
                      Alzheimer's disease (AD) in a meaningful way, influential
                      factors (i.e. training set) and prediction across groups
                      such as APOE e4 (APOE4) genotype as well as associations to
                      dementia-related biomarkers should be explored. Therefore,
                      we examined the association of APOE4 and various PRSs, based
                      on training sets that utilized differing AD definitions,
                      with incident AD and all-cause dementia (ACD) within 17
                      years, and with levels of phosphorylated tau181 (P-tau181),
                      neurofilament light (NfL), and glial fibrillary acidic
                      protein (GFAP) in blood. Secondarily, effect modification by
                      APOE4 status and sex was examined.In this prospective,
                      population-based cohort study and nested case-control study,
                      9,940 participants in Germany were enrolled between 2000 and
                      2002 by their general practitioners and followed for up to
                      17 years. Participants were included in this study if
                      dementia status and genetic data were available. A subsample
                      of participants additionally had measurements of P-tau181,
                      NfL, and GFAP obtained from blood samples. Cox and logistic
                      regression analyses were used to assess the association of
                      genetic risk (APOE genotype and PRSnoAPOE) with incident
                      ACD/AD and log-transformed blood levels of P-tau181, NfL,
                      and GFAP.Five thousand seven hundred sixty-five participants
                      $(54\%$ female, aged 50-75years at baseline) were included
                      in this study, of whom 464 received an all-cause dementia
                      diagnosis within 17 years. The PRSs were not more predictive
                      of dementia than APOE4. An APOE4 specific relationship was
                      apparent with PRSs only exhibiting associations to dementia
                      among APOE4 carriers. In the nested case-control study
                      including biomarkers (n = 712), APOE4 status and polygenic
                      risk were significantly associated to levels of GFAP in
                      blood.The use of PRSs may be beneficial for increased
                      precision in risk estimates among APOE4 carriers. While
                      APOE4 may play a crucial etiological role in initial disease
                      processes such as Aβ deposition, the PRS may be an
                      indicator of further disease drivers as well as astrocyte
                      activation. Further research is necessary to confirm these
                      findings, especially the association to GFAP.},
      keywords     = {Alzheimer’s disease (Other) / Blood-biomarkers (Other) /
                      Polygenic risk scores (Other)},
      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:37516890},
      pmc          = {pmc:PMC10386275},
      doi          = {10.1186/s13195-023-01277-8},
      url          = {https://inrepo02.dkfz.de/record/277864},
}