2024
Leveraging a large language model to predict protein phase transition: A physical, multiscale, and interpretable approach
Frank M, Ni P, Jensen M, Gerstein M. Leveraging a large language model to predict protein phase transition: A physical, multiscale, and interpretable approach. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2320510121. PMID: 39110734, PMCID: PMC11331094, DOI: 10.1073/pnas.2320510121.Peer-Reviewed Original ResearchConceptsProtein phase transitionsAssociated with reduced gene expressionProtein structure predictionAlzheimer's disease-related proteinsDisease-related proteinsAlzheimer's diseaseProtein sequencesSequence variantsStructure predictionAmyloid aggregatesProtein designGene expressionAge-related diseasesNatural defense mechanismsSoluble stateProteinDefense mechanismsBiophysical featuresAlzheimerSequenceAmyloidVariantsExpressionLanguage modelComputational frameworkAmyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes
Lesman-Segev O, Golan Shekhtman S, Springer R, Livny A, Lin H, Yuxia O, Zadok M, Ganmore I, Heymann A, Hoffmann C, Domachevsky L, Schnaider Beeri M. Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes. Scientific Reports 2024, 14: 2741. PMID: 38302529, PMCID: PMC10834442, DOI: 10.1038/s41598-024-53043-x.Peer-Reviewed Original ResearchConceptsNon-demented older adultsCognitive functionLower cognitive functionAmyloid burdenCognitive declineOlder adultsAssociations of small vessel diseaseAssociated with cognitive functionCognitive Decline studyAssociated with lower cognitive functionTreating cognitive declineAssociated with cognitive declineType 2 diabetesGray matterAssociation of amyloidIsrael DiabetesGM volumeAssess cognitionMeasures of small vessel diseaseWhite matter hyperintensitiesAlzheimer's disease biomarkersCognitionDecline studiesSmall vessel diseaseDiabetes-related characteristics
2023
Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging
Kim C, Diez I, Bueichekú E, Ahn S, Montal V, Sepulcre J. Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging. Journal Of Neuroscience 2023, 44: e0488232023. PMID: 38123362, PMCID: PMC10869152, DOI: 10.1523/jneurosci.0488-23.2023.Peer-Reviewed Original ResearchConceptsHarvard Aging Brain StudyCognitive changesCognitive declineAssociated with cognitive changesAssociated with early cognitive declineAging Brain StudyEarly cognitive declineTau depositionCognitive scoresBrain studiesHuman brainTau pathologyOlder adultsTau accumulationTau associationImpaired associationAD symptomsClinical trajectoryCortical patternsTauBraak stageSpatiotemporal levelsTemporal accumulationBraakFuture increasesLung endothelium, tau, and amyloids in health and disease
Balczon R, Lin M, Voth S, Nelson A, Schupp J, Wagener B, Pittet J, Stevens T. Lung endothelium, tau, and amyloids in health and disease. Physiological Reviews 2023, 104: 533-587. PMID: 37561137, PMCID: PMC11281824, DOI: 10.1152/physrev.00006.2023.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsEnd-organ dysfunctionLung endotheliumLower respiratory tract infectionsRespiratory tract infectionsAlveolar-capillary barrierLung capillary endotheliumTract infectionsImmune responseNeurocognitive dysfunctionBarrier integrityProtein tauLung capillariesInfectionCapillary endotheliumDysfunctionEpithelial cellsEndotheliumTau variantsVascular nicheTauHost-pathogen interactionsType ICytotoxic activityCytotoxicAmyloid variantsPrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patterns
2022
Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals
Hong Y, Kim C, Lee J, Sepulcre J. Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals. Scientific Reports 2022, 12: 14307. PMID: 35995824, PMCID: PMC9395408, DOI: 10.1038/s41598-022-18325-2.Peer-Reviewed Original ResearchConceptsApolipoprotein epsilon 4Apolipoprotein epsilon 4 alleleAlzheimer's Disease Neuroimaging InitiativeApolipoprotein epsilon 4 carriersTau burdenAmyloid depositsAPOE4 non-carriersAssociated with amyloid depositionPresence of ApoE4 alleleCross-sectional studyRegional tau burdenAssess correlationsCognitively normal participantsIncreased amyloid burdenNormal cognitive functionCognitively normal older individualsStandardized uptake value ratioEpsilon 4AD-related biomarkersAPOE4 alleleTau depositionCortical thicknessAmyloidCarrier statusAllelesAlzheimer disease neuropathology in a patient previously treated with aducanumab
Plowey ED, Bussiere T, Rajagovindan R, Sebalusky J, Hamann S, von Hehn C, Castrillo-Viguera C, Sandrock A, Budd Haeberlein S, van Dyck CH, Huttner A. Alzheimer disease neuropathology in a patient previously treated with aducanumab. Acta Neuropathologica 2022, 144: 143-153. PMID: 35581440, PMCID: PMC9217863, DOI: 10.1007/s00401-022-02433-4.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesLong-term extensionStandard uptake value ratioAlzheimer's diseaseAmyloid positron emission tomographyBraak stage VPhase 1b studyPhospho-tau immunohistochemistryPostmortem neuropathologic examinationSpecies of AβAD neuropathologic changeFirst autopsy reportAlzheimer's disease neuropathologyUptake value ratioAmyloid PET scanMild Alzheimer's diseasePositron emission tomographyLast doseReactive microgliaNeuropathologic evidenceNeuropathologic examinationPlacebo armImaging abnormalitiesMonthly dosesNeuropathologic changes
2021
Amyloid-Associated Depression—or Not?
van Dyck CH, O'Dell RS, Mecca AP. Amyloid-Associated Depression—or Not? Biological Psychiatry 2021, 89: 737-738. PMID: 33766236, PMCID: PMC8396710, DOI: 10.1016/j.biopsych.2021.02.008.Peer-Reviewed Original Research
2020
Advances in PET-Based Cardiac Amyloid Radiotracers
Gallegos C, Miller EJ. Advances in PET-Based Cardiac Amyloid Radiotracers. Current Cardiology Reports 2020, 22: 40. PMID: 32430600, DOI: 10.1007/s11886-020-01284-3.Peer-Reviewed Original ResearchConceptsPositron emission tomographyCardiac amyloidosisAmyloid depositionAmyloid radiotracersCardiac amyloid depositionCare of patientsTransthyretin cardiac amyloidosisCardiac imaging techniquesCongo red stainingPurpose of ReviewWeNovel positron emission tomographyEndomyocardial biopsyImaging featuresAmyloid depositsUnmet needInvasive methodEmission tomographyAmyloidosisGold standardAdditive valueRed stainingBiopsyFurther dataDiagnosisRecent studiesAmyloid: From Starch to Finish
Krystal HL, Ross DA, Mecca AP. Amyloid: From Starch to Finish. Biological Psychiatry 2020, 87: e23-e24. PMID: 32299582, PMCID: PMC7449531, DOI: 10.1016/j.biopsych.2020.02.1182.Peer-Reviewed Original Research
2019
Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
Perov S, Lidor O, Salinas N, Golan N, Fligelman E, Deshmukh M, Willbold D, Landau M. Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents. PLOS Pathogens 2019, 15: e1007978. PMID: 31469892, PMCID: PMC6748439, DOI: 10.1371/journal.ppat.1007978.Peer-Reviewed Original ResearchConceptsDisease-associated amyloidsStructural insightsCross-seeded fibrillationMajor curli subunitBiofilm formationHost cell adhesionCurli amyloid fibrilsAmyloid-forming segmentAlzheimer's disease-associated amyloidAnti-amyloid compoundsCurli formationCurli subunitsPathological amyloidsAmyloidogenic regionsMicrobial sourcesEnvironmental stressorsAmyloid interactionsCell adhesionAnti-biofilm agentsΒ-sheetCsgANeurodegenerative diseasesSalmonella typhimuriumStructural linkStructural resemblance
2018
Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology
Grothe M, Sepulcre J, Gonzalez-Escamilla G, Jelistratova I, Schöll M, Hansson O, Teipel S, Initiative A. Molecular properties underlying regional vulnerability to Alzheimer’s disease pathology. Brain 2018, 141: 2755-2771. PMID: 30016411, PMCID: PMC6113636, DOI: 10.1093/brain/awy189.Peer-Reviewed Original ResearchConceptsRegional gene expression profilesGene expression profilesAlzheimer's disease pathologyExpression profilesPathophysiological mechanism of Alzheimer's diseaseDisease pathologyAlzheimer's diseaseAmyloid depositsExpression levelsMechanisms of Alzheimer's diseaseHuman brain transcriptomeGene Set Enrichment AnalysisTau kinasesAlzheimer's Disease Neuroimaging InitiativeMicroarray measurementsTau proteinMAPT expressionAllen Brain AtlasGene setsAmyloid precursorBrain transcriptomeRas-ERKNeurofibrillary degenerationRegionally selective vulnerabilityMitochondrial respirationTime Course of Common Clinical Manifestations in Patients with Transthyretin Cardiac Amyloidosis: Delay From Symptom Onset to Diagnosis
Papoutsidakis N, Miller EJ, Rodonski A, Jacoby D. Time Course of Common Clinical Manifestations in Patients with Transthyretin Cardiac Amyloidosis: Delay From Symptom Onset to Diagnosis. Journal Of Cardiac Failure 2018, 24: 131-133. PMID: 29305186, DOI: 10.1016/j.cardfail.2017.12.005.Peer-Reviewed Original Research
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaquesCurrent insight in the localized insulin-derived amyloidosis (LIDA): clinico-pathological characteristics and differential diagnosis
Ansari AM, Osmani L, Matsangos AE, Li QK. Current insight in the localized insulin-derived amyloidosis (LIDA): clinico-pathological characteristics and differential diagnosis. Pathology - Research And Practice 2017, 213: 1237-1241. PMID: 28935176, DOI: 10.1016/j.prp.2017.08.013.Peer-Reviewed Original ResearchConceptsInsulin-derived amyloidosisSystemic amyloidosisDiabetic patientsGlycemic controlDifferential diagnosisAccurate diagnosisAggressive systemic therapyBlood glycemic controlCommon side effectsCase series studyClinico-pathological characteristicsNon-surgical approachSubcutaneous insulin injectionsPrimary cutaneous amyloidosisAnti-insulin antibodiesAutonomic neuropathyInsulin requirementsClinical suspicionKey diagnostic featuresRare complicationSystemic therapySurgical excisionSurgical interventionCase reportInsulin injectionsPET Imaging for Early Detection of Alzheimer’s Disease From Pathologic to Physiologic Biomarkers
Bao W, Jia H, Finnema S, Cai Z, Carson RE, Huang YH. PET Imaging for Early Detection of Alzheimer’s Disease From Pathologic to Physiologic Biomarkers. PET Clinics 2017, 12: 329-350. PMID: 28576171, DOI: 10.1016/j.cpet.2017.03.001.Peer-Reviewed Original ResearchMultimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load
Grothe M, Villeneuve S, Dyrba M, Bartrés-Faz D, Wirth M, Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Liu E, Green R, Montine T, Petersen R, Aisen P, Gamst A, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Jack C, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Morris J, Cairns N, Taylor-Reinwald L, Trojanowki J, Shaw L, Lee V, Korecka M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder P, Molchan S, Kaye J, Quinn J, Lind B, Dolen S, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Ances B, Carroll M, Leon S, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, Leyla deToledo-Morrell P, Shah R, Duara R, Varon D, Roberts, CNA P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon M, Glodzik L, De Santi S, Doraiswamy P, Petrella J, Coleman R, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Apostolova L, Lu P, Bartzokis G, Silverman D, Graff-Radford, MBBCH N, Parfitt F, Johnson H, Farlow M, Hake A, Matthews B, Herring S, van Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Robin Hsiung G, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam M, Lipowski K, Wu C, Johnson N, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Frey M, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Bwayo S, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee T, Bartha D, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Saykin A, Santulli R, Schwartz E, Sink K, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Longmire C, Spicer K, Finger E, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz S, Boles Ponto L, Shim H, Smith K, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj B. Multimodal characterization of older APOE2 carriers reveals selective reduction of amyloid load. Neurology 2017, 88: 569-576. PMID: 28062720, PMCID: PMC5304459, DOI: 10.1212/wnl.0000000000003585.Peer-Reviewed Original ResearchConceptsAPOE2 carriersGray matter volumeAmyloid loadAmyloid pathologyAged brainAPOE2 alleleDisease Neuroimaging InitiativeMatter volumeCross-sectional multimodalRegional amyloid loadTypical age-related increaseAlzheimer's disease biomarkersVoxel-wise analysisAge-related increaseAlzheimer's Disease Neuroimaging InitiativeApoE3 homozygotesInterest-based analysisFluorodeoxyglucose PETTau pathologyAmyloid depositionAPOE3 genotypeParietal metabolismAV45-PETHippocampal volumeBrain changes
2016
TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 90: 724-739. PMID: 27196974, PMCID: PMC4898967, DOI: 10.1016/j.neuron.2016.05.003.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAxonal dystrophyAmyloid depositsAD-like miceHuman AD tissueLate-onset Alzheimer's diseaseNovel therapeutic strategiesTREM2 deficiencyTau hyperphosphorylationAD tissueMicroglia processesPharmacological modulationCompact plaquesTherapeutic strategiesHigh-resolution confocalTREM2 mutationsTREM2Barrier functionMiceGreater surface exposureAmyloid fibrilsHaplodeficiencyPlaquesDiseaseDystrophy
2015
Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms
Botsios S, Tittman S, Manuelidis L. Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms. Virulence 2015, 6: 787-801. PMID: 26556670, PMCID: PMC4826107, DOI: 10.1080/21505594.2015.1098804.Peer-Reviewed Original ResearchConceptsInfectious titerInnate immune responseHuman CJDResistant virusesIatrogenic infectionGT1 cellsBrain changesImmune responseInfectious agentsTSE agentsScrapie agentCJDPrion protein amyloidSheep scrapieVirulent microbesInfectious particlesMin exposureIntrinsic resistanceTreatmentTitersPrP amyloidScrapieAmyloidCultured cellsDeep proteomic analysisValidating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue
Marquié M, Normandin M, Vanderburg C, Costantino I, Bien E, Rycyna L, Klunk W, Mathis C, Ikonomovic M, Debnath M, Vasdev N, Dickerson B, Gomperts S, Growdon J, Johnson K, Frosch M, Hyman B, Gómez-Isla T. Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue. Annals Of Neurology 2015, 78: 787-800. PMID: 26344059, PMCID: PMC4900162, DOI: 10.1002/ana.24517.Peer-Reviewed Original ResearchConceptsTau filamentsAlzheimer brainsTDP-43Paired helical filamentsDNA-binding proteinsIn vitro binding assaysFrontotemporal lobar degeneration-tauBinding to tau lesionsDNA-binding protein 43Tauopathy brainsHelical filamentsBrain tau pathologyTau pathologyTau lesionsSubstrate-specificBinding proteinPostmortem brain tissueCerebral amyloid angiopathyPhosphor-screen autoradiographyOff-target bindingB-amyloidAlzheimer's diseaseBinding assaysTauProtein 43
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