Chronic head injury promotes tau and amyloid‐beta pathology and accelerates cognitive decline in a humanized knock‐in model of Alzheimer's disease
Chiasseu M, Fesharaki A, Saito T, Saido T, Strittmatter S. Chronic head injury promotes tau and amyloid‐beta pathology and accelerates cognitive decline in a humanized knock‐in model of Alzheimer's disease. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047623.Peer-Reviewed Original ResearchMild traumatic brain injuryChronic head injuryHead injuryMorris water maze testAmyloid-beta pathologyAccumulation of amyloidAge-matched miceWater maze testTraumatic brain injuryNovel object recognitionProtein gene mutationsEnvironmental risk factorsAlzheimer's disease symptomsIba1 expressionCortical AβAlzheimer pathologyPhospho-tauClinical manifestationsAD pathologyCortical impactorAD pathogenesisRisk factorsBrain injuryApp NLMaze testGene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in
Chiasseu M, Fesharaki-Zadeh A, Saito T, Saido TC, Strittmatter SM. Gene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in. Neurobiology Of Disease 2020, 145: 105059. PMID: 32858147, PMCID: PMC7572902, DOI: 10.1016/j.nbd.2020.105059.Peer-Reviewed Original ResearchConceptsMild traumatic brain injuryTraumatic brain injuryAlzheimer's diseaseBrain injuryGene-environment interactionsMild closed head injuryMorris water maze testAge-matched wild-type controlsStrong unmet needAccumulation of amyloidAge-matched miceClosed head injuryWater maze testNovel object recognitionPersistent cognitive deficitsProtein gene mutationsIba1 expressionWild-type controlsPhospho-tauClinical manifestationsAD pathologyAD symptomsHead injuryAD pathogenesisRisk factorsFyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy
Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathologica Communications 2020, 8: 96. PMID: 32611392, PMCID: PMC7329553, DOI: 10.1186/s40478-020-00976-9.Peer-Reviewed Original ResearchConceptsRepetitive closed head injuriesMemory deficitsPhospho-tau accumulationChronic variable stressPersistent memory deficitsP301S transgenic miceClosed head injuryFyn inhibitionPassive avoidance learningFyn kinaseGlial activationPhospho-tauPresynaptic markersSynapse lossTau accumulationHead injurySynapse densityPhosphorylated tauTherapeutic benefitTransgenic miceBehavioral improvementTrauma modelTauopathiesSpatial memoryAvoidance learning