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@ARTICLE{Franzmeier:155552,
      author       = {Franzmeier, Nicolai and Ossenkoppele, Rik and Brendel,
                      Matthias and Rubinski, Anna and Smith, Ruben and Kumar, Atul
                      and Mattsson-Carlgren, Niklas and Strandberg, Olof and
                      Duering, Marco and Bürger, Katharina and Dichgans, Martin
                      and Hansson, Oskar and Ewers, Michael and Initiative, ,
                      Alzheimer's Disease Neuroimaging and study, the Swedish
                      BioFINDER},
      title        = {{T}he {BIN}1 rs744373 {A}lzheimer's disease risk {SNP} is
                      associated with faster {A}β-associated tau accumulation and
                      cognitive decline.},
      journal      = {Alzheimer's and dementia},
      volume       = {18},
      number       = {1},
      issn         = {1552-5279},
      address      = {Hoboken, NJ},
      publisher    = {Wiley},
      reportid     = {DZNE-2021-00730},
      pages        = {103-115},
      year         = {2022},
      abstract     = {The BIN1 rs744373 single nucleotide polymorphism (SNP) is a
                      key genetic risk locus for Alzheimer's disease (AD)
                      associated with tau pathology. Because tau typically
                      accumulates in response to amyloid beta (Aβ), we tested
                      whether BIN1 rs744373 accelerates Aβ-related tau
                      accumulation.We included two samples (Alzheimer's Disease
                      Neuroimaging Initiative [ADNI], n = 153; Biomarkers for
                      Identifying Neurodegenerative Disorders Early and Reliably
                      [BioFINDER], n = 63) with longitudinal 18 F-Flortaucipir
                      positron emission tomography (PET), Aβ biomarkers, and
                      longitudinal cognitive assessments. We assessed whether BIN1
                      rs744373 was associated with faster tau-PET accumulation at
                      a given level of Aβ and whether faster BIN1
                      rs744373-associated tau-PET accumulation mediated cognitive
                      decline.BIN1 rs744373 risk-allele carriers showed faster
                      global tau-PET accumulation (ADNI/BioFINDER,
                      P < .001/P < .001). We found significant Aβ by rs744373
                      interactions on global tau-PET change (ADNI: β/standard
                      error [SE] = 0.42/0.14, P = 0.002; BioFINDER:
                      β/SE = -0.35/0.15, P = .021), BIN1 risk-allele carriers
                      showed accelerated tau-PET accumulation at higher Aβ
                      levels. In ADNI, rs744373 effects on cognitive decline were
                      mediated by faster global tau-PET accumulation
                      (β/SE = 0.20/0.07, P = .005).BIN1-associated AD risk is
                      potentially driven by accelerated tau accumulation in the
                      face of Aβ.},
      keywords     = {Adaptor Proteins, Signal Transducing: genetics / Aged /
                      Alzheimer Disease: genetics / Amyloid beta-Peptides:
                      cerebrospinal fluid / Amyloid beta-Peptides: metabolism /
                      Biomarkers: cerebrospinal fluid / Brain: metabolism /
                      Cognitive Dysfunction: metabolism / Female / Humans / Male /
                      Nuclear Proteins: genetics / Polymorphism, Single Nucleotide
                      / Positron-Emission Tomography / Tumor Suppressor Proteins:
                      genetics / tau Proteins: metabolism / Alzheimer's disease
                      (Other) / BIN1 (Other) / amyloid (Other) / tau (Other)},
      cin          = {AG Höglinger 2 / AG Simons},
      ddc          = {610},
      cid          = {I:(DE-2719)1111015 / I:(DE-2719)1110008},
      pnm          = {351 - Brain Function (POF4-351) / 353 - Clinical and Health
                      Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34060233},
      doi          = {10.1002/alz.12371},
      url          = {https://pub.dzne.de/record/155552},
}