2025
Growth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer’s dementia continuum: an [18 F] AV-45 study
Nemati R, Sohrabi-Ashlaghi A, Saberian P, Sadeghi M, Mardani S, Abadi A, Yaghoobpoor A, Heydari A, Khoshroo N, Rahnama Y, Mayeli M, Nasiri H. Growth associated protein 43 (GAP-43) predicts brain amyloidosis in Alzheimer’s dementia continuum: an [18 F] AV-45 study. BMC Neurology 2025, 25: 134. PMID: 40170060, PMCID: PMC11959801, DOI: 10.1186/s12883-025-04140-5.Peer-Reviewed Original ResearchConceptsAssociated with Alzheimer's diseaseMild cognitive impairmentMild cognitive impairment groupStandardized uptake value ratioAlzheimer's Disease Neuroimaging InitiativePET standardized uptake value ratioEarly stages of ADAmyloid-betaGAP-43Tau pathologyGAP-43 levelsAssociated proteinSynaptic dysfunctionStages of ADAV-45Mild cognitive impairment stageBrain amyloidosisAlzheimer's diseaseDementia continuumCognitive impairmentProtein 43Synaptic plasticityDiagnosis of ADProteinGrowth-associated proteinUncovering cerebral blood flow patterns corresponding to Amyloid-beta accumulations in patients across the Alzheimer’s disease continuum using the arterial spin labeling
Daneshpour A, Nasiri H, Motamed A, Heidarzadeh N, Fard A, Koleini S, Fakhimi F, Abiri L, Mayeli M, Sadeghi M. Uncovering cerebral blood flow patterns corresponding to Amyloid-beta accumulations in patients across the Alzheimer’s disease continuum using the arterial spin labeling. Neurological Sciences 2025, 46: 2081-2090. PMID: 39838256, DOI: 10.1007/s10072-025-07992-4.Peer-Reviewed Original ResearchConceptsMild cognitive impairmentSubjective memory complaintsMethodsWe analyzed dataAmyloid-betaDisease continuumAD participantsLinear regression modelsMultiple linear regression modelMemory complaintsRight inferior parietal cortexUnadjusted analysisCaudal middle frontal cortexRight lateral occipital cortexEducation levelAlzheimer's disease continuumCerebral blood flowAmyloid-beta accumulationArterial spin labelingLeft pars triangularisMiddle frontal cortexInferior parietal cortexAD dementiaLateral occipital cortexHigher cognitive functionsCognitive declineThe etiology and prevention of early‐stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques
Datta D, Arnsten A. The etiology and prevention of early‐stage tau pathology in higher cortical circuits: Insights from aging rhesus macaques. Alzheimer's & Dementia 2025, 21: e14477. PMID: 39776253, PMCID: PMC11848412, DOI: 10.1002/alz.14477.Peer-Reviewed Original ResearchConceptsAged macaquesAged rhesus macaquesP-tauTau hyperphosphorylationCortical circuitsAmyloid-beta generationSoluble phosphorylated tauCognitive deficitsAged monkeysSoluble hyperphosphorylated tauSporadic Alzheimer's diseaseAssociation cortexEarly-stage pathologyRhesus macaquesIncreased ABCalcium dysregulationCalcium regulationToxic to neuronsHyperphosphorylated tauAmyloid-betaCortexInflammatory signalingP-tau217 levelsTau pathologyPhosphorylated tauInflammaging, Neuroinflammation, and Synaptic Damage in Alzheimer's Disease
Carnevale L, Lipton S. Inflammaging, Neuroinflammation, and Synaptic Damage in Alzheimer's Disease. 2025, 303-314. DOI: 10.1016/b978-0-323-95702-1.00491-7.Peer-Reviewed Original ResearchAmyloid-betaAlzheimer's diseaseAmyloid-beta precursor proteinProteins amyloid-betaNeuronal healthDiscovery of mutationsAlzheimer's disease casesGenome sequencePresenilin-1Precursor proteinProtein functionAlzheimer's disease researchImmune signalingLipid transportProgressive neurodegenerative diseaseAlzheimer's disease patientsGenetic causeApolipoprotein E4Genes related to lipid transportSynaptic damageStress-mediated alterationsNeurodegenerative diseasesDisease pathologyProteinAlzheimer
2024
Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum
Trelle A, Young C, Vossler H, Benitez J, Cody K, Mendiola J, Swarovski M, Le Guen Y, Feinstein I, Butler R, Channappa D, Romero A, Park J, Shahid‐Besanti M, Corso N, Chau K, Smith A, Skylar‐Scott I, Yutsis M, Fredericks C, Tian L, Younes K, Kerchner G, Deutsch G, Davidzon G, Sha S, Henderson V, Longo F, Greicius M, Wyss‐Coray T, Andreasson K, Poston K, Wagner A, Mormino E, Wilson E. Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum. Alzheimer's & Dementia 2024, 21: e14442. PMID: 39713875, PMCID: PMC11848181, DOI: 10.1002/alz.14442.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseCognitive declinePositron emission tomographyAmyloid-betaTau accumulationAmyloid positivityHippocampal-dependent memoryAlzheimer's disease spectrumAmyloidAmyloid accumulationTau burdenAb accumulationRisk of cognitive declineSensitive to memoryTau positron emission tomographyAlzheimer's Disease Research CenterPredicting cognitive declineAlzheimerTauScalable biomarkersAD continuumCerebral amyloid accumulationCross-sectional associationsCI individualsAccumulationIs there Evidence for a Continued Benefit for Long‐Term Lecanemab Treatment? A Benefit/Risk Update from Long‐Term Efficacy, Safety and Biomarker Data
van Dyck C, Sperling R, Dhadda S, Li D, Hersch S, Irizarry M, Kramer L. Is there Evidence for a Continued Benefit for Long‐Term Lecanemab Treatment? A Benefit/Risk Update from Long‐Term Efficacy, Safety and Biomarker Data. Alzheimer's & Dementia 2024, 20: e092094. PMCID: PMC11713166, DOI: 10.1002/alz.092094.Peer-Reviewed Original ResearchOpen-label extensionAlzheimer's diseaseBrain regions of individualsMultiple measures of cognitionMeasures of cognitionAmyloid-betaTau spreadingMarkers of amyloidAD studiesRegions of individualsBrain regionsHuman IgG1 monoclonal antibodyPhase 2 studyMonths of treatmentLong-term efficacyLecanemabLonger-term dosingIgG1 monoclonal antibodyInfusion reactionsMultiple measuresRandomized studyExamining 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 reserveMidlifeAPOE 𝜀4‐related blood–brain barrier breakdown is associated with microstructural abnormalities
Reas E, Solders S, Tsiknia A, Triebswetter C, Shen Q, Rivera C, Andrews M, Alderson‐Myers A, Brewer J. APOE 𝜀4‐related blood–brain barrier breakdown is associated with microstructural abnormalities. Alzheimer's & Dementia 2024, 20: 8615-8624. PMID: 39411970, PMCID: PMC11667544, DOI: 10.1002/alz.14302.Peer-Reviewed Original ResearchAPOE4 carriersAlzheimer's diseaseAmyloid-negative individualsAmyloid-betaAmyloid-positive individualsApoE4AD cascadeAmyloidBlood-brain barrierAPOE 4Magnetic resonance imagingBrain microstructureAbsence of cognitive declinePreclinical ADLinear regression assessed associationsAmyloid positivityNeurodegenerative changesCortical gray matterCognitive declineMicrostructural abnormalitiesAssociated with microstructural abnormalitiesCognitive statusApoNeurodegenerationOlder adultsDeletion of miR‐33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice
Tate M, Wijeratne H, Kim B, Philtjens S, You Y, Lee D, Gutierrez D, Sharify D, Wells M, Perez‐Cardelo M, Doud E, Fernandez‐Hernando C, Lasagna‐Reeves C, Mosley A, Kim J. Deletion of miR‐33, a regulator of the ABCA1–APOE pathway, ameliorates neuropathological phenotypes in APP/PS1 mice. Alzheimer's & Dementia 2024, 20: 7805-7818. PMID: 39345217, PMCID: PMC11567857, DOI: 10.1002/alz.14243.Peer-Reviewed Original ResearchAmyloid-betaAlzheimer's diseaseMicroglial migrationAmyloid mouse modelMiR-33Multi-omics studiesABCA1 levelsPotential drug targetsIncreased ABCA1 protein levelsMicroRNA-33ApoE lipidationProteomic changesRNA sequencingMulti-OmicsNeuropathological phenotypeAmyloid pathologyInhibition of miR-33APP/PS1 micePhagocytosis in vitroRare variantsApolipoprotein EDrug targetsABCA1 protein levelsAmyloidPlaque depositionCT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease
Lizama B, Williams C, North H, Pandey K, Duong D, Di V, Mecca A, Blennow K, Zetterberg H, Levey A, Grundman M, van Dyck C, Caggiano A, Seyfried N, Hamby M. CT1812 biomarker signature from a meta‐analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 6860-6880. PMID: 39166791, PMCID: PMC11485314, DOI: 10.1002/alz.14152.Peer-Reviewed Original ResearchVolumetric magnetic resonance imagingMagnetic resonance imagingPharmacodynamic biomarkersMeta-analysisClinical developmentCerebrospinal fluidPhase 2 clinical trialResonance imagingAlzheimer's diseaseMechanism of actionClinical trialsTandem mass tag-mass spectrometryClinical cohortMild to moderate ADCandidate biomarkersCT1812CohortBiomarker signaturesBiomarkersProteomic findingsUnbiased analysisNetwork analysisAmyloid-betaSynaptic biologyBiological impactHumanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology
Miller B, Kim S, Cao K, Mehta H, Thumaty N, Kumagai H, Iida T, McGill C, Pike C, Nurmakova K, Levine Z, Sullivan P, Yen K, Ertekin‐Taner N, Atzmon G, Barzilai N, Cohen P. Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology. Aging Cell 2024, 23: e14153. PMID: 38520065, PMCID: PMC11258485, DOI: 10.1111/acel.14153.Peer-Reviewed Original ResearchAPOE4 carriersAPOE4 alleleAmyloid beta clearanceMouse model of amyloidosisAlzheimer's diseaseAmyloid-beta pathologyIn silico analysisAmyloid-beta accumulationMitochondrial-derived peptideGenes associated with phagocytosisResistance to ADModel of amyloidosisAmyloid-betaBeta pathologyAssociated with longevitySilico analysisHumaninFactors to Alzheimer's diseaseApoE4Transcriptomic assessmentAmino acidsInfluence longevityAllelesPhagocytosisAshkenazi descentAPOE ε4 is associated with decreased synaptic density in cognitively impaired participants
He K, Li B, Wang J, Wang Y, You Z, Chen X, Chen H, Li J, Huang Q, Guo Q, Huang Y, Guan Y, Chen K, Zhao J, Deng Y, Xie F. APOE ε4 is associated with decreased synaptic density in cognitively impaired participants. Alzheimer's & Dementia 2024, 20: 3157-3166. PMID: 38477490, PMCID: PMC11095422, DOI: 10.1002/alz.13775.Peer-Reviewed Original ResearchApolipoprotein E4Tau pathologyAlzheimer's diseaseApo E4AD biomarkersAPOE e4 allele carriersAmyloid-betaEffects of apolipoprotein E4Synaptic lossAPOE e4 alleleSynaptic densitySynaptic density lossNon-carriersE4 alleleE4 allele carriersE4 genotypeTauGenotypesPositron emission tomographyAllele carriersMedial temporal lobeAllelesAmyloidEffect of APOE E4Cognitively impaired participantsAntioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro
Bae S, Lee W, Bak S, Lee S, Hwang S, Kim G, Koo B, Park S, Yoo H, Kim C, Kang H, Oh T, Kim Y. Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro. International Journal Of Molecular Sciences 2024, 25: 2313. PMID: 38396988, PMCID: PMC10889506, DOI: 10.3390/ijms25042313.Peer-Reviewed Original ResearchConceptsFormation of neurofibrillary tanglesNeurofibrillary tanglesAlzheimer's diseaseImpaired clearance of amyloid betaSignaling pathwayClearance of amyloid betaAMPK Signaling PathwayActivate signaling pathwaysAlzheimer's disease in vivoInhibition of cell apoptosisCause of dementiaAmyloid-betaHT-22 cellsNeuritic plaquesIn vitroMitochondrial dysfunctionOxidative stressCell apoptosisDisease in vivoROS generationHT-22Prevent ADAMPKDisorders in vivoProtein levels“Dark” Pathways of Protein Transnitrosylation Injure Synapses in Alzheimer’s Disease: Mechanism and Potential Treatment
LIPTON S. “Dark” Pathways of Protein Transnitrosylation Injure Synapses in Alzheimer’s Disease: Mechanism and Potential Treatment. 2024, pl. DOI: 10.14869/toxpt.51.1.0_pl.Peer-Reviewed Original ResearchAlzheimer's diseaseDisruption of protein functionUbiquitin-protein hydrolaseS-nitrosylationS-nitrosylation reactionLoss of synapsesCorrelated to cognitive declineGuanosine triphosphataseMitochondrial fragmentationAD brainProtein functionAmyloid-betaAggregated proteinsProtein hydrolaseSynapse lossSynaptic lossBioenergetic compromiseSynaptic damageTransnitrosylation reactionsProteinUCH-L1Environmental factorsEnzymeAlzheimerCascade
2023
Age‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model
Nelson R, Rangaraju S, Rayaprolu S, Kumar P, Espinosa‐Garcia C, Xiao H. Age‐Dependent Changes in Perineuronal Nets and Associated Parvalbumin Interneurons in the 5xFAD Amyloidosis Mouse Model. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.083101.Peer-Reviewed Original ResearchPV+ neuronsWild typePerineuronal netsAlzheimer's diseaseAD-like pathologyCo-localizationMouse modelAmyloid-betaFast-spiking interneuronsEarly amyloidosisRegulate synaptic transmissionSynaptic maintenanceExtracellular matrix structurePlaque proximityAge-dependent mannerMonths of agePhysiological roleImmunofluorescence microscopyNeuronal roleNeurodegenerative diseasesParvalbumin-positiveParvalbumin interneuronsAge-dependent changesSynaptic transmissionProximal dendritesThe VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology
Lau S, Wu W, Wong H, Ouyang L, Qiao Y, Xu J, Lau J, Wong C, Jiang Y, Holtzman D, Fu A, Ip N. The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology. Nature Aging 2023, 3: 1219-1236. PMID: 37735240, PMCID: PMC10570140, DOI: 10.1038/s43587-023-00491-1.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsAlzheimer's diseaseMicroglial chemotaxisAmeliorate AD pathologyDisease pathologyAlzheimer's disease pathologyAmyloid-betaFunctional screeningPlaque-associatedMicroglial clearanceAD pathologyExtrinsic signalsPhagocytic clearanceExacerbate disease pathologyMolecular patternsIL-33ChemotaxisMicroglial functionAlzheimerVCAM1Interleukin-33Higher cerebrospinal fluid levelsApoPathwayMicrogliaReceptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology
Lau S, Fu A, Ip N. Receptor–ligand interaction controls microglial chemotaxis and amelioration of Alzheimer's disease pathology. Journal Of Neurochemistry 2023, 166: 891-903. PMID: 37603311, DOI: 10.1111/jnc.15933.Peer-Reviewed Original ResearchConceptsDanger-associated molecular patternsMicroglial chemotaxisAD pathogenesisAlzheimer's diseaseMicroglial functionRepertoire of surface receptorsHyperphosphorylated tauAlzheimer's disease pathologyAmyloid-betaMolecular machineryMicroglial receptorsReceptor-ligand interactionsPhagocytic clearanceReceptor-ligand axisMolecular patternsSurface receptorsFunctional transitionDisease pathologyChemotaxisBrain homeostasisAberrant synaptic pruningClearance activityCritical stepsReceptorsAmyloidAn IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE‐ε4 in Alzheimer’s disease
JIANG Y, Zhou X, Wong H, Li O, Ip F, Chau V, Lau S, Wu W, Wong D, Seo H, Fu W, Lai N, Chen Y, Chen Y, Tong E, Mok V, Kwok T, Mok K, Shoai M, Lehallier B, Moran‐Losada P, O’Brien E, Porter T, Laws S, Hardy J, Wyss‐Coray T, Masters C, Fu A, Ip N, Initiative A. An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE‐ε4 in Alzheimer’s disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.064428.Peer-Reviewed Original ResearchGenome-wide association studiesGenetic regulationAlzheimer's diseaseGenome-wide association study analysisGenetic variantsPathogenesis of Alzheimer's diseaseAD risk genesDisease-causing roleAPOE-e4 carriersAssociation studiesGenetic variationAmyloid-betaRisk genesMicroglial clearanceBrains of patientsBackground genetic factorsAD therapySevere neurodegenerationMicroglial dysfunctionAb accumulationMicroglial functionDecoy receptorGenetic factorsAPOE-e4IL1RL1
2022
An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease
Jiang Y, Zhou X, Wong H, Ouyang L, Ip F, Chau V, Lau S, Wu W, Wong D, Seo H, Fu W, Lai N, Chen Y, Chen Y, Tong E, Mok V, Kwok T, Mok K, Shoai M, Lehallier B, Losada P, O’Brien E, Porter T, Laws S, Hardy J, Wyss-Coray T, Masters C, Fu A, Ip N. An IL1RL1 genetic variant lowers soluble ST2 levels and the risk effects of APOE-ε4 in female patients with Alzheimer’s disease. Nature Aging 2022, 2: 616-634. PMID: 37117777, PMCID: PMC10154240, DOI: 10.1038/s43587-022-00241-9.Peer-Reviewed Original ResearchConceptsAssociated with Alzheimer's diseaseGenetic variantsGenome-wide association analysisDisease-causing roleCRISPR-Cas9 genome editingEuropean-descent populationsAlzheimer's diseaseMouse transcriptomeDisease-causing factorsGenetic variationAmyloid-betaEnhancer elementsAssociation analysisDownregulated genesAD riskGenome editingMendelian randomization analysisLower AD riskDecoy receptorProtein levelsAPOE-e4Female individualsProteinVariantsModulation of microglial activation
2021
Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging
Kim C, Montal V, Diez I, Orwig W, Initiative A, Sepulcre J. Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging. Human Brain Mapping 2021, 42: 2990-3004. PMID: 33955621, PMCID: PMC8193537, DOI: 10.1002/hbm.25350.Peer-Reviewed Original ResearchConceptsCognitively normal older adultsAmyloid-betaPathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseTau depositionPositron emission tomographyGeneral cognitive impairmentTau neurofibrillary tanglesAlzheimer's diseaseNormal older adultsOlder adultsAmyloid-beta depositionCognitive test scoresTau pathogenesisAD vulnerable areasNeurofibrillary tanglesHeteromodal areasTau accumulationCognitive changesCognitive deteriorationCognitive impairmentCognitive declinePathological hallmarkPreclinical ADCognitive level
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