Caspase-6 knock-out using CRISPR/Cas9 improves cognitive behavior in the 3xTg mouse model of Alzheimer's disease

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by global cognitive decline involving memory, orientation, judgment, and reasoning and is the most common form of dementia in the elderly. Caspases, a family of cysteine proteases, are major mediators of apoptosis and inflammation. Active Caspase-6 (Casp6) is abundant in neuropil threads, neuritic plaques and neurofibrillary tangles of AD brains. Our goal will be to knockout Casp6 activity using the CRISPR/Cas9 system and thus attempt to alleviate the pathological degradation caused by its activated pathway.