Age-related neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are the most common cause of morbidity in the Veteran population. Medical costs for U.S. Veterans of Iraq and Afghanistan could be enormous because of differences between these wars and previous conflicts due to today’s Veterans surviving injuries that would have been fatal in previous wars, and "polytraumatic" injuries that require decades of costly physical and social rehabilitation. With no prevention or treatment, individuals with neurodegenerative conditions could reach 11-16 million by 2050. In addition to age-related neurodegeneration, depression among the elderly has been estimated to increase health care costs by 50% and increase outpatient costs by 43 to 52% in these individuals compared to non-depressed patients. With this growing Veteran population is an increase in chronic health conditions, and social and financial burdens on their families and the health care system. Neurodegeneration diseases are closely associated with decreased neuronal signaling, mitochondrial dysfunction, loss of synapses and neuromuscular junctions. Since receiving the VA CDA in 2009, the Head laboratory has focused on targeting molecular mechanisms (via genetic and/or pharmacologic interventions) to evoke functional neuronal and synaptic plasticity to improve cognitive and motor function in the neurodegenerative brain and spinal cord respectively. As a result of continuous funding from the VA (3 Merits since 2011) and NIH (NINDS R01 2011), in 2012 Dr. Head was bestowed the Presidential Early Career Awards for Scientists and Engineers (PECASE) through the Department of Veterans Affairs, which is the highest honor given by the United States Government to early-stage scientist and engineers. Specifically, the Head laboratory investigates how caveolin (Cav), a cholesterol binding and scaffolding protein within membrane/lipid rafts (MLRs), regulates synaptic signaling, mitochondrial function, and neuroplasticity in neuronal models in vitro using human neurons derived from iPSCs and in animal models of neurodegeneration such as AD and ALS. Cav-1 is a cholesterol-binding and membrane protein that is essential for MLR formation and MLR-localization of neurotrophin receptors and synaptic proteins necessary for synaptic function and neuroplasticity. Dr. Head engineered a genetic construct that contains a neuron- targeted promoter (synapsin) to drive the expression of Cav-1 (termed SynCav1) specifically in neurons to evoke neuroprotection and functional plasticity in the setting of disease or following traumatic injury (work funded by NINDS, VA, and DoD). Dr. Head patented this novel gene therapy through the U.S. Patent Office in March 2015 (U.S. Patent No. 8,969,077 B2: Neuronal specific targeting of caveolin expression to restore synaptic signaling and improve cognitive function in the neurodegenerative brain and motor function in spinal cord) of which the ...