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000276479 0247_ $$2doi$$a10.1523/JNEUROSCI.1408-24.2024
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000276479 1001_ $$0P:(DE-2719)9002356$$aFischer, Larissa$$b0$$eFirst author$$udzne
000276479 245__ $$aPrecuneus Activity during Retrieval Is Positively Associated with Amyloid Burden in Cognitively Normal Older APOE4 Carriers.
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000276479 520__ $$aThe precuneus is a site of early amyloid-beta (Aβ) accumulation. Previous cross-sectional studies reported increased precuneus fMRI activity in older adults with mild cognitive deficits or elevated Aβ. However, longitudinal studies in early Alzheimer's disease (AD) are lacking and the relationship to the Apolipoprotein-E (APOE) genotype is unclear. Investigating the PREVENT-AD dataset, we assessed how baseline and longitudinal precuneus activity during successful memory retrieval relates to future Aβ and tau burden and change in memory performance. We further studied the moderation by APOE4 genotype. We included 165 older adults (age, 62.8 ± 4.4 years; 113 female; 66 APOE4 carriers) who were cognitively normal at baseline with a family history of AD. All participants performed task-fMRI at baseline and underwent 18F-flortaucipir-PET and 18F-NAV4694-Aβ-PET on average 5 years later. We found that higher baseline activity and greater longitudinal increase in precuneus activity were associated with higher Aβ burden in APOE4 carriers but not noncarriers. We observed no effects of precuneus activity on tau burden. Finally, APOE4 noncarriers with low baseline precuneus activity exhibited better longitudinal performance in an independent memory test compared with (1) noncarriers with higher baseline activity and (2) APOE4 carriers. Our findings suggest that higher task-related precuneus activity during memory retrieval at baseline and over time are associated with greater Aβ burden in cognitively normal APOE4 carriers. Our results further indicate that the absence of 'hyperactivation' and the absence of the APOE4 allele is related with better future cognitive outcomes in cognitively normal older adults at risk for AD.
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000276479 650_7 $$2Other$$aAPOE4
000276479 650_7 $$2Other$$aamyloid
000276479 650_7 $$2Other$$aepisodic memory retrieval
000276479 650_7 $$2Other$$afunctional hyperactivity
000276479 650_7 $$2Other$$amultimodal neuroimaging
000276479 650_7 $$2Other$$aprecuneus
000276479 650_7 $$2NLM Chemicals$$aApolipoprotein E4
000276479 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000276479 650_7 $$2NLM Chemicals$$atau Proteins
000276479 650_2 $$2MeSH$$aHumans
000276479 650_2 $$2MeSH$$aFemale
000276479 650_2 $$2MeSH$$aMale
000276479 650_2 $$2MeSH$$aApolipoprotein E4: genetics
000276479 650_2 $$2MeSH$$aAged
000276479 650_2 $$2MeSH$$aParietal Lobe: metabolism
000276479 650_2 $$2MeSH$$aParietal Lobe: diagnostic imaging
000276479 650_2 $$2MeSH$$aParietal Lobe: physiopathology
000276479 650_2 $$2MeSH$$aMiddle Aged
000276479 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000276479 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000276479 650_2 $$2MeSH$$aHeterozygote
000276479 650_2 $$2MeSH$$aPositron-Emission Tomography
000276479 650_2 $$2MeSH$$aMental Recall: physiology
000276479 650_2 $$2MeSH$$aLongitudinal Studies
000276479 650_2 $$2MeSH$$aCognition: physiology
000276479 650_2 $$2MeSH$$atau Proteins: metabolism
000276479 650_2 $$2MeSH$$atau Proteins: genetics
000276479 7001_ $$0P:(DE-2719)9002180$$aMolloy, Eóin N.$$b1
000276479 7001_ $$00000-0001-5218-3337$$aPichet Binette, Alexa$$b2
000276479 7001_ $$0P:(DE-2719)9000804$$aVockert, Niklas$$b3
000276479 7001_ $$0P:(DE-2719)9001692$$aMarquardt, Jonas$$b4
000276479 7001_ $$0P:(DE-2719)9002548$$aPacha Pilar, Andrea$$b5$$udzne
000276479 7001_ $$0P:(DE-2719)2812799$$aKreißl, Michael$$b6$$udzne
000276479 7001_ $$aRemz, Jordana$$b7
000276479 7001_ $$aTremblay-Mercier, Jennifer$$b8
000276479 7001_ $$00000-0002-8018-4545$$aPoirier, Judes$$b9
000276479 7001_ $$aRajah, Maria Natasha$$b10
000276479 7001_ $$00000-0003-2338-0467$$aVilleneuve, Sylvia$$b11
000276479 7001_ $$aGroup, PREVENT-AD Research$$b12$$eCollaboration Author
000276479 7001_ $$0P:(DE-2719)2811815$$aMaass, Anne$$b13$$eFirst author
000276479 773__ $$0PERI:(DE-600)1475274-8$$a10.1523/JNEUROSCI.1408-24.2024$$gVol. 45, no. 6, p. e1408242024 -$$n6$$pe1408242024$$tThe journal of neuroscience$$v45$$x0270-6474$$y2025
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