2024
APOE4 moderates the association between cerebral small vessel disease and cortical tau accumulation in midlife
Espinoza L, Scott M, Beiser A, Banh A, Philip V, Ghosh S, Thibault E, Maillard P, Decarli C, Fakhri G, Johnson K, Seshadri S, Satizabal C. APOE4 moderates the association between cerebral small vessel disease and cortical tau accumulation in midlife. Alzheimer's & Dementia 2024, 20: e091824. PMCID: PMC11714429, DOI: 10.1002/alz.091824.Peer-Reviewed Original ResearchAPOE-e4 genotypeAPOE-e4APOE-e4 carriersBiomarkers of cerebral small vessel diseaseIncreased risk of ADSignificant associationFramingham Heart StudyThird Generation cohortsRegional tauCerebral small vessel diseaseCognitively healthy participantsRisk of ADMiddle-aged adultsBorderline significant associationCardiovascular risk factorsSmall vessel diseaseDementia onsetNo significant associationHeart StudyPotential confoundersAlzheimer's diseaseLinear regression modelsE4 genotypeTau accumulationIncreased riskExamining early cerebral amyloid beta and tau accumulation in association with cognition in a predominantly middle‐aged cohort
Gonzales M, O’Donnell A, Ghosh S, Thibault E, Tanner J, Satizabal C, Decarli C, Fakhri G, Johnson K, Beiser A, Seshadri S, Pase M. Examining early cerebral amyloid beta and tau accumulation in association with cognition in a predominantly middle‐aged cohort. Alzheimer's & Dementia 2024, 20: e087431. PMCID: PMC11716433, DOI: 10.1002/alz.087431.Peer-Reviewed Original ResearchStratified analysisPoorer visuospatial functionFramingham Heart StudyTau positron emission tomographyPositron emission tomographyMiddle-aged cohortApolipoprotein E4 statusCommunity-based cohortTau accumulationAssociated with cognitive declineVisuospatial functionLow cognitive reserveAssociated with cognitionAmyloid-betaHeart StudyOlder adultsE4 statusLinear regression modelsCerebral amyloid-betaPoor cognitionMeasures of ABCognitive AssessmentCollege degreeCognitive reserveMidlife
2023
Locus coeruleus metabolic changes as a predictor of tau accumulation and cognitive decline
Koops E, Dutta J, Becker A, Van Egroo M, Riphagen J, Hanseeuw B, Sperling R, Fakhri G, Johnson K, Jacobs H. Locus coeruleus metabolic changes as a predictor of tau accumulation and cognitive decline. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.073715.Peer-Reviewed Original ResearchBeta-amyloidTau pathologyAlzheimer's diseaseNeuropathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseP-tauBeta-amyloid levelsP-tau accumulationMetabolic turnoverAccumulation of p-tauMarkers of AD progressionTau formationLocus coeruleusAD pathological changesTau accumulationNeuropathological hallmarksAD progressionPhosphorylated-tauPositron emission tomographyLate stageLociPairwise analysisMetabolismPair-wise differencesFDG-PET signal
2022
Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes
Montal V, Diez I, Kim C, Orwig W, Bueichekú E, Gutiérrez-Zúñiga R, Bejanin A, Pegueroles J, Dols-Icardo O, Vannini P, El-Fakhri G, Johnson K, Sperling R, Fortea J, Sepulcre J. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Science Translational Medicine 2022, 14: eabn7273. PMID: 35895837, PMCID: PMC9942690, DOI: 10.1126/scitranslmed.abn7273.Peer-Reviewed Original ResearchConceptsTau spreadingIntracellular accumulation of tau proteinAccumulation of tau proteinAlzheimer's diseasePathological tau accumulationGenetic gradientGenetic dataTau proteinNeurofibrillary tanglesSynaptic genesTau accumulationGenetic traitsGenesDrug development strategiesExpression gradientIntracellular accumulationTauExpressionCognitively normal older participantsHuman brain cortexTanglesProteinApoTraitsAlzheimer
2020
Tracking the origin of tau spread in the brain
Jacobs H, Becker A, Kwong K, Uquillas F, Papp K, Properzi M, Rentz D, Fakhri G, Sperling R, Johnson K. Tracking the origin of tau spread in the brain. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.037501.Peer-Reviewed Original ResearchEntorhinal cortexMemory declineLocus coeruleusHarvard Aging Brain StudyPosterior cingulate cortexProspective memory declineAD-related cognitive declineMedial temporal lobeAging Brain StudyTau spreadingAlzheimer's diseaseCingulate cortexLimbic regionsNeuropsychological assessmentCingulate regionsTau PET imagingLC integrityCognitive changesTau accumulationMediation analysisTemporal lobeEntorhinal tauIncreased ABCognitive declineBrain studies
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