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Search: onr:"swepub:oai:lup.lub.lu.se:6dd5b944-ec60-47d6-bcff-e831b3d930f7" > The BIN1 rs744373 A...

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  • Franzmeier, NicolaiUniversity Hospital Munich (author)

The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2021-06
  • Wiley,2022

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:6dd5b944-ec60-47d6-bcff-e831b3d930f7
  • https://lup.lub.lu.se/record/6dd5b944-ec60-47d6-bcff-e831b3d930f7URI
  • https://doi.org/10.1002/alz.12371DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Introduction: 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. Methods: 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 18F-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. Results: 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). Discussion: BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ossenkoppele, RikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam(Swepub:lu)ri1513os (author)
  • Brendel, MatthiasMunich Cluster for Systems Neurology,University Hospital Munich (author)
  • Rubinski, AnnaUniversity Hospital Munich (author)
  • Smith, RubenLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-rsm (author)
  • Kumar, AtulLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)at5381ku (author)
  • Mattsson-Carlgren, NiklasLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-nmn (author)
  • Strandberg, OlofLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)teor-osn (author)
  • Duering, MarcoUniversity Hospital Munich,University of Basel (author)
  • Buerger, KatharinaGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich (author)
  • Dichgans, MartinGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich,Munich Cluster for Systems Neurology (author)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (author)
  • Ewers, MichaelGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich (author)
  • University Hospital MunichKlinisk minnesforskning (creator_code:org_t)
  • Alzheimer's Disease Neuroimaging Initiative
  • Swedish BioFinder Study

Related titles

  • In:Alzheimer's and Dementia: Wiley18:1, s. 103-1151552-52601552-5279

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