Inhibition of APP Secretases as a Therapy for Traumatic Brain Injury

APP secretase inhibitors, currently in AD clinical trials, may prove effective in treating TBI, as may other interventions that reduce amyloid-beta levels.

Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer disease (AD). The increased risk could be a result of increased postinjury production and accumulation of the amyloid-beta (Aβ) peptide, the main constituent of the amyloid plaques found in AD-affected brain and also in 30% of patients with TBI. Previous studies have demonstrated beneficial effects of post-TBI use of caspase inhibitors (Exp Neurol 2006; 197:437) and other modulators of Aβ precursor protein (APP) metabolism and Aβ production. The hypothesis underlying this research was that Aβ reduction would prevent the peptide's accumulation and aggregation into soluble oligomers and insoluble fibrils, which are neurotoxic. In this study, researchers targeted two en…

Reviewing Authors

Milos D. Ikonomovic, MD

Steven T. DeKosky, MD

Inhibition of APP Secretases as a Therapy for Traumatic Brain Injury

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Reviewing Authors