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The BIN1 rs744373 A...
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Franzmeier, NicolaiUniversity Hospital Munich
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The BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline
- Article/chapterEnglish2022
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LIBRIS-ID:oai:lup.lub.lu.se:6dd5b944-ec60-47d6-bcff-e831b3d930f7
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https://lup.lub.lu.se/record/6dd5b944-ec60-47d6-bcff-e831b3d930f7URI
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https://doi.org/10.1002/alz.12371DOI
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Language:English
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Summary in:English
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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.
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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)
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Brendel, MatthiasMunich Cluster for Systems Neurology,University Hospital Munich
(author)
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Rubinski, AnnaUniversity Hospital Munich
(author)
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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)
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Kumar, AtulLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)at5381ku
(author)
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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)
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Strandberg, OlofLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)teor-osn
(author)
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Duering, MarcoUniversity Hospital Munich,University of Basel
(author)
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Buerger, KatharinaGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
(author)
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Dichgans, MartinGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich,Munich Cluster for Systems Neurology
(author)
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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)
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Ewers, MichaelGerman Center for Neurodegenerative Diseases (DZNE), Bonn,University Hospital Munich
(author)
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University Hospital MunichKlinisk minnesforskning
(creator_code:org_t)
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Alzheimer's Disease Neuroimaging Initiative
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Swedish BioFinder Study
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In:Alzheimer's and Dementia: Wiley18:1, s. 103-1151552-52601552-5279
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Franzmeier, Nico ...
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Rubinski, Anna
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Smith, Ruben
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Mattsson-Carlgre ...
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Strandberg, Olof
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