Laskowitz, Daniel TSong, PingpingWang, HaichenMace, BrianSullivan, Patrick MVitek, Michael PDawson, Hana N2011-04-152010-11https://hdl.handle.net/10161/3293Cognitive impairment is common following traumatic brain injury (TBI), and neuroinflammatory mechanisms may predispose to the development of neurodegenerative disease. Apolipoprotein E (apoE) polymorphisms modify neuroinflammatory responses, and influence both outcome from acute brain injury and the risk of developing neurodegenerative disease. We demonstrate that TBI accelerates neurodegenerative pathology in double-transgenic animals expressing the common human apoE alleles and mutated amyloid precursor protein, and that pathology is exacerbated in the presence of the apoE4 allele. The administration of an apoE-mimetic peptide markedly reduced the development of neurodegenerative pathology in mice homozygous for apoE3 as well as apoE3/E4 heterozygotes. These results demonstrate that TBI accelerates the cardinal neuropathological features of neurodegenerative disease, and establishes the potential for apoE mimetic therapies in reducing pathology associated with neurodegeneration.en-USAmyloid beta-PeptidesAnimalsApolipoproteins EBlotting, WesternBrainBrain InjuriesCytokinesEnzyme-Linked Immunosorbent AssayGenetic TherapyGliosisHumansImmunohistochemistryMaleMiceMice, TransgenicMotor ActivityNeurodegenerative DiseasesPlatelet-Derived Growth FactorPolymorphism, GeneticPsychomotor PerformanceRNA, MessengerTumor Necrosis Factor-alphatau ProteinsJournal article1557-9042