Amyloid Protective Hypothesis: A Cure for Alzheimers Disease

Statistics are staggering: in the U.S. alone. nearly six million affected. sixth most common cause of death. over $300 billion per year in direct care costs and billions more in unpaid care. billions of dollars in research and Alzheimers disease (AD) has no effective therapy to reverse let alone arrest progression. AD is the only common disease increasing every year. Described over a century ago and with thousands of talented researchers studying it. AD has no effective drugs to prevent. treat or cure it. For 20 years I have argued against the dominant theory. amyloid cascade hypothesis putting amyloid (A) as the cause based on rare familial cases of AD where mutations in A processing are statistically linked to AD and mice and cell studies that indicated A is toxic. Put simply. the dominant theory has been that removing amyloid is the answer. and it has not worked. For over 20 years I have presented evidence that A is instead a protective response to AD. and the genetics support a central role. not a cause. Vaccine and imaging studies in sporadic or familial AD patients show A removal is without clinical benefit. ruling out causality and more importantly demonstrating that A is NOT a toxic response. Instead. our studies place A as central and a drug target for therapeutic intervention. The proposed studies build on our recent novel findings that A is an antioxidant. The focus of our proposal expands upon our unexpected finding. while working with the University of Oxford. of metallic iron and copper in A deposits in the human brain. the first report in all of biology. Our proposed studies will define the antioxidant mechanism. determine its role in blocking cell death. and open the pathway to effective drug development.