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000154260 0247_ $$2doi$$a10.1016/j.cub.2020.08.042
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000154260 037__ $$aDZNE-2021-00114
000154260 041__ $$aEnglish
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000154260 1001_ $$0P:(DE-2719)2810615$$aLee, Hwee Ling$$b0$$eFirst author
000154260 245__ $$aGenetic Alzheimer's Disease Risk Affects the Neural Mechanisms of Pattern Separation in Hippocampal Subfields.
000154260 260__ $$aLondon$$bCurrent Biology Ltd.$$c2020
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000154260 520__ $$aThe hippocampal subfields perform distinct operations during acquisition, differentiation, and recollection of episodic memories, and deficits in pattern separation are among the first symptoms of Alzheimer's disease (AD). We investigated how hippocampal subfields contribute to pattern separation and how this is affected by Apolipoprotein-E (APOE), the strongest AD genetic risk factor. Using ultra-high-field (7T) functional magnetic resonance imaging (fMRI), APOE-ε3-ε3 carriers predominantly recruited cornu ammonis 3 (CA3) during a spatial mnemonic discrimination task, whereas APOE-ε3-ε4 and APOE-ε3-ε2 carriers engaged CA3 and dentate gyrus (DG) to the same degree. Specifically, APOE-ε3-ε4 carriers showed reduced pattern separation in CA3, whereas APOE-ε3-ε2 carriers exhibited increased effects in DG and pattern separation-related functional connectivity between DG and CA3. Collectively, these results demonstrate that AD genetic risk alters hemodynamic responses in young pre-symptomatic individuals, paving the way for development of biomarkers for preclinical AD.
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000154260 650_7 $$2Other$$a7T
000154260 650_7 $$2Other$$aAPOE genotype
000154260 650_7 $$2Other$$aCA3
000154260 650_7 $$2Other$$adentate gyrus
000154260 650_7 $$2Other$$aepisodic memory
000154260 650_7 $$2Other$$afunctional connectivity
000154260 650_7 $$2Other$$ahippocampal subfields
000154260 650_7 $$2Other$$apattern separation
000154260 650_2 $$2MeSH$$aAdult
000154260 650_2 $$2MeSH$$aAlleles
000154260 650_2 $$2MeSH$$aAlzheimer Disease: diagnosis
000154260 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000154260 650_2 $$2MeSH$$aAlzheimer Disease: physiopathology
000154260 650_2 $$2MeSH$$aApolipoproteins E: genetics
000154260 650_2 $$2MeSH$$aApolipoproteins E: metabolism
000154260 650_2 $$2MeSH$$aBrain Mapping
000154260 650_2 $$2MeSH$$aCA3 Region, Hippocampal: diagnostic imaging
000154260 650_2 $$2MeSH$$aCA3 Region, Hippocampal: physiopathology
000154260 650_2 $$2MeSH$$aDentate Gyrus: diagnostic imaging
000154260 650_2 $$2MeSH$$aDentate Gyrus: physiopathology
000154260 650_2 $$2MeSH$$aFemale
000154260 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000154260 650_2 $$2MeSH$$aGenotyping Techniques
000154260 650_2 $$2MeSH$$aHealthy Volunteers
000154260 650_2 $$2MeSH$$aHeterozygote
000154260 650_2 $$2MeSH$$aHumans
000154260 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000154260 650_2 $$2MeSH$$aMale
000154260 650_2 $$2MeSH$$aMemory, Episodic
000154260 650_2 $$2MeSH$$aRisk Factors
000154260 650_2 $$2MeSH$$aYoung Adult
000154260 7001_ $$0P:(DE-2719)2810697$$aStirnberg, Rüdiger$$b1
000154260 7001_ $$0P:(DE-2719)9001491$$aWu, Sichu$$b2$$udzne
000154260 7001_ $$0P:(DE-2719)9001478$$aWang, Xin$$b3$$udzne
000154260 7001_ $$0P:(DE-2719)2810538$$aStöcker, Tony$$b4
000154260 7001_ $$aJung, Sonja$$b5
000154260 7001_ $$aMontag, Christian$$b6
000154260 7001_ $$0P:(DE-HGF)0$$aAxmacher, Nikolai$$b7
000154260 773__ $$0PERI:(DE-600)2019214-9$$a10.1016/j.cub.2020.08.042$$gVol. 30, no. 21, p. 4201 - 4212.e3$$n21$$p4201 - 4212.e3$$tCurrent biology$$v30$$x0960-9822$$y2020
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