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 signalAssociation of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease
Prokopiou P, Engels-Domínguez N, Schultz A, Sepulcre J, Koops E, Papp K, Marshall G, Normandin M, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease. Neurology 2023, 101: e1206-e1217. PMID: 37491329, PMCID: PMC10516269, DOI: 10.1212/wnl.0000000000207646.Peer-Reviewed Original ResearchConceptsLC activityMemory declineLocus coeruleusCognitive declineEC tauHarvard Aging Brain StudyHuman neuroimaging studiesSteeper memory declineNoradrenergic brainstem nucleiLongitudinal cognitive dataFunctional MRI dataTau depositionAging Brain StudyPreclinical Alzheimer's diseaseTau progressionCortical tau depositionElevated beta-amyloidInterventions promoting resilienceMild cognitive impairmentExecutive dysfunctionExecutive functionNeuroimaging studiesTau spreadingTemporal cortexCognitive composite
2022
Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals.
Prokopiou P, Engels N, Schneider C, Schultz A, Sepulcre J, Riphagen J, Koops E, Papp K, Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.067706.Peer-Reviewed Original ResearchMemory declineLC activityLocus coeruleusEC tauEntorhinal cortexLC phasic activationAssociated with memory declineFace-name pairsMediation effectHarvard Aging Brain StudySteeper memory declineExposure to noveltyAssociated with tau depositionInferior temporal lobeSpatial patterns of tauAging Brain StudyPreclinical Alzheimer's diseaseCortical tau depositionTau depositionFusiform cortexMemory testInsular cortexMixed-effects analysisMediation analysisInferior temporalLower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals
Prokopiou P, Engels-Domínguez N, Papp K, Scott M, Schultz A, Schneider C, Farrell M, Buckley R, Quiroz Y, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals. Nature Communications 2022, 13: 1571. PMID: 35322012, PMCID: PMC8943159, DOI: 10.1038/s41467-022-28986-2.Peer-Reviewed Original ResearchConceptsCognitive declineLC activityLC-FCFunctional connectivityLocus coeruleusAssociated with altered neuronal activityNeuronal activityFace-name paradigmAD-related cognitive declineHuman imaging researchIn vivo neuronal activityLongitudinal cognitive dataAssociated with cognitive declineBeta-amyloid-PETIndividuals at-riskAlzheimer's diseaseCognitively unimpaired older individualsBeta-amyloidSubcortical regionsFunctional MRICognitive dataNeurofibrillary tauImaging researchHippocampusCognition
2021
Locus coeruleus integrity as a proxy of initial tau burden: in vivo versus ex vivo observations
Jacobs H, Becker A, Kwong K, Engels N, Prokopiou P, Papp K, Properzi M, Hampton O, Sanchez J, Rentz D, Fakhri G, Normandin M, Bennett D, Sperling R, Johnson K. Locus coeruleus integrity as a proxy of initial tau burden: in vivo versus ex vivo observations. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.056391.Peer-Reviewed Original ResearchHarvard Aging Brain StudyMini-Mental State ExaminationLC integrityLocus coeruleusMini-Mental State Examination scoreNeuronal densityTangle densityLocus coeruleus integrityAging Brain StudyTau pathologyAlzheimer's diseaseAD-related processesVertex-wiseTemporal regionsBraak stageLC measurementsMini-MentalMCI/AD patientsState ExaminationBrain studiesPiB-PET imagingTau-PETPET measurementsPiB-PETTangle burdenIn vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline
Jacobs H, Becker J, Kwong K, Engels-Domínguez N, Prokopiou P, Papp K, Properzi M, Hampton O, d'Oleire Uquillas F, Sanchez J, Rentz D, El Fakhri G, Normandin M, Price J, Bennett D, Sperling R, Johnson K. In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline. Science Translational Medicine 2021, 13: eabj2511. PMID: 34550726, PMCID: PMC8641759, DOI: 10.1126/scitranslmed.abj2511.Peer-Reviewed Original ResearchConceptsLC integrityLongitudinal cognitive measuresCognitive measuresLocus coeruleusIndicators of Alzheimer's disease pathologyLocus coeruleus integrityMedial temporal lobeTangle densityRush Memory and Aging ProjectBraak stageMemory and Aging ProjectHyperphosphorylated tau aggregatesAlzheimer's diseaseB-amyloidAD-related processesMemory declineCognitive dysfunctionDisease pathologyCognitive trajectoriesTemporal lobeLC neuronsPostmortem correlationsCognitive declineEntorhinal cortexPreclinical AD
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