In addition to loss of memory, symptoms of Alzheimer's disease (AD) include apathy and circadian dysregulation. We identified a critical pathway from the retina to the brain that regulates locus coeruleus (LC), a key brain system for memory, motivation and circadian rhythms. Notably, LC degeneration is one of the first indicators of AD pathologies. We propose to use the chemogenetic tool Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to regulate this retina-LC circuit and test its efficacy as a novel therapy to treat AD.
The proposed studies employ designer receptors to stimulate retinal ganglion cells and modulate activity of a brain region important in the etiology and symptoms of Alzheimer's disease. This is a minimally invasive approach to control such important neural networks without the need for brain surgery. This research could have great impact on understanding and treating Alzheimer's disease and other neuropsychiatric disorders.