Anthony N Brady Professor of Pathology & Cell Biology, Yale School of Medicine
Director, Boyer Center for Molecular Medicine
I was born in New York City, attended Yale College and Yale Medical School, and received the D. Phil degree in experimental pathology from Oxford University. After residency training in pathology at Washington University, I spent a post-doctoral year at Rockefeller University working with George Palade, who inspired me to study the red cell membrane. After six years at the NIH I returned to Yale in 1972, where I eventually became the Anthony N. Brady Professor of Pathology and chair of the department, a position I held until 1990, when I became Director of the Boyer Center for Molecular Medicine, a position I still hold.
Most of my professional career focused on the study of membrane proteins of the human erythrocyte. Over a twenty-year period my lab sequenced one of the first trans-membrane proteins (glycophorin A) and identified and studied many of the proteins that make up the erythrocyte membrane skeleton, including spectrin, protein 4.1, and oligomeric forms of actin. These studies led to a greater understanding of the patho-physiology of hemolytic anemias.
When my wife, Dr. Sally Marchesi, developed Alzheimer’s disease in the late 1990’s, I was totally unaware of the basis for this devastating disease. Since then it has been my entire scientific focus. I follow the field with hawk-like intensity and have recently published an opinion piece in the FASEB Journal. This article summarized the evidence that has led to the now widely accepted Amyloid Hypothesis as the cause of Alzheimer’s dementia. My analysis of the field leads me to believe that amyloid is an important component of its pathogenesis, but not the only one. Many have suggested that oxidative damage and inflammatory reactions also play contributing roles. We now realize that clinically evident dementia is preceded by several decades of an unknown pathogenic process or processes that are initially asymptomatic but lead over time to neuronal dysfunction and eventually neuronal cell death. I hypothesized that sometime during the pre-dementia period reactive oxygens and inflammation generate low abundant, somatic mutations that damage small blood vessels, leading to localized ischemia and neuronal dysfunction and amyloid dysregulation. Amyloid accumulations in critical areas of the brain ultimately lead to end-stage Alzheimer’s disease and clinical dementia.