Novel Compounds for Reducing Brain A-Beta Levels via Enhanced Systemic Clearance

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is characterized by progressively worsening dementia eventually leading to death. It affects over five million people in the United States and costs the healthcare system over 200 billion per year. Currently there is no available therapy for slowing, reversing or preventing the disease. There is strong evidence suggesting that AD starts with the accumulation of the 4.5 kDa peptide, amyloid beta (A?), in the brain leading to concentration-dependent A? self-assembly into neurotoxic oligomers. A? accumulation in sporadic AD is related to a decreased net clearance rate of A? from the brain rather than A? overproduction. Despite the strong correlation between A? accumulation and AD progression, most amyloid-targeted therapeutic approaches have failed to demonstrate significant clinical benefits. However, most A?-targeted therapies have focused on removing specific forms of A? (e.g. plaques or oligomers), inhibiting A? production, or shifting the equili