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000155552 0247_ $$2doi$$a10.1002/alz.12371
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000155552 1001_ $$0P:(DE-HGF)0$$aFranzmeier, Nicolai$$b0$$eCorresponding author
000155552 245__ $$aThe BIN1 rs744373 Alzheimer's disease risk SNP is associated with faster Aβ-associated tau accumulation and cognitive decline.
000155552 260__ $$aHoboken, NJ$$bWiley$$c2022
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000155552 520__ $$aThe BIN1 rs744373 single nucleotide polymorphism (SNP) is a key genetic risk locus for Alzheimer's disease (AD) associated with tau pathology. Because tau typically accumulates in response to amyloid beta (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-related tau accumulation.We included two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI], n = 153; Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably [BioFINDER], n = 63) with longitudinal 18 F-Flortaucipir positron emission tomography (PET), Aβ biomarkers, and longitudinal cognitive assessments. We assessed whether BIN1 rs744373 was associated with faster tau-PET accumulation at a given level of Aβ and whether faster BIN1 rs744373-associated tau-PET accumulation mediated cognitive decline.BIN1 rs744373 risk-allele carriers showed faster global tau-PET accumulation (ADNI/BioFINDER, P < .001/P < .001). We found significant Aβ by rs744373 interactions on global tau-PET change (ADNI: β/standard error [SE] = 0.42/0.14, P = 0.002; BioFINDER: β/SE = -0.35/0.15, P = .021), BIN1 risk-allele carriers showed accelerated tau-PET accumulation at higher Aβ levels. In ADNI, rs744373 effects on cognitive decline were mediated by faster global tau-PET accumulation (β/SE = 0.20/0.07, P = .005).BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.
000155552 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0
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000155552 650_7 $$2Other$$aAlzheimer's disease
000155552 650_7 $$2Other$$aBIN1
000155552 650_7 $$2Other$$aamyloid
000155552 650_7 $$2Other$$atau
000155552 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: genetics
000155552 650_2 $$2MeSH$$aAged
000155552 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000155552 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000155552 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000155552 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000155552 650_2 $$2MeSH$$aBrain: metabolism
000155552 650_2 $$2MeSH$$aCognitive Dysfunction: metabolism
000155552 650_2 $$2MeSH$$aFemale
000155552 650_2 $$2MeSH$$aHumans
000155552 650_2 $$2MeSH$$aMale
000155552 650_2 $$2MeSH$$aNuclear Proteins: genetics
000155552 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000155552 650_2 $$2MeSH$$aPositron-Emission Tomography
000155552 650_2 $$2MeSH$$aTumor Suppressor Proteins: genetics
000155552 650_2 $$2MeSH$$atau Proteins: metabolism
000155552 7001_ $$aOssenkoppele, Rik$$b1
000155552 7001_ $$aBrendel, Matthias$$b2
000155552 7001_ $$0P:(DE-2719)2812415$$aRubinski, Anna$$b3$$udzne
000155552 7001_ $$aSmith, Ruben$$b4
000155552 7001_ $$aKumar, Atul$$b5
000155552 7001_ $$aMattsson-Carlgren, Niklas$$b6
000155552 7001_ $$aStrandberg, Olof$$b7
000155552 7001_ $$aDuering, Marco$$b8
000155552 7001_ $$0P:(DE-2719)2811351$$aBürger, Katharina$$b9$$udzne
000155552 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b10$$udzne
000155552 7001_ $$aHansson, Oskar$$b11
000155552 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b12$$udzne
000155552 7001_ $$0P:(DE-HGF)0$$aInitiative, , Alzheimer's Disease Neuroimaging$$b13
000155552 7001_ $$0P:(DE-HGF)0$$astudy, the Swedish BioFINDER$$b14
000155552 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz.12371$$gp. alz.12371$$n1$$p103-115$$tAlzheimer's and dementia$$v18$$x1552-5279$$y2022
000155552 8564_ $$uhttps://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12371
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