Neurodegenerative diseases in general and Alzheimer's disease (AD) in particular have an enormous public health impact. Moreover, the incidence is projected to escalate in the next 30 years. The development of effective therapies and/or preventive measures for these diseases would alleviate the loss of the quality of life for individuals who suffer these tragic disorders and unburden the society of their economic impact. To this effect, developing new therapeutic strategies to decrease the levels of Amyloid-beta, the disease causing protein in AD, is important. Increasing levels of steroid hormones is known to be beneficial for cognition and memory, two functional aspects that are affected in AD. This proposed study aims at harnessing these neuroprotective effects of estrogens and androgens to alleviate the neuropathological features of AD. ACADIA pharmaceuticals have discovered an androgen receptor agonist, ACP-105, which works as a non-steroidal selective androgen receptor modulator (SARM). SARMs can modulate in a tissue-selective manner, minimizing the deleterious effects of the natural or synthetic hormones. We intend using ACP-105 and an agonist of the estrogen receptor beta (ERbeta1) to test their effects on the clearance of Abeta in a cell culture and mouse models of AD. The cell culture model will be a novel model to screen this class of synthetic ligands for steroid receptors in the context of Abeta and experiments in mouse models will validate their efficacy. ACADIA will partner with the neuroscience expertise from Lunds Universitet to mobilize this proposed study, which will create avenues for future clinical trials.