2010 Awardee
Rudy J. Castellani, M.D.

Rudy J. Castellani, Jr., MD, received his medical degree from Wayne State University in 1990, after which he trained in anatomic pathology at Wayne State University’s Detroit Medical Center, followed by a neuropathology fellowship at Case Western Reserve University and University Hospitals of Cleveland, under the mentorship of Drs. Pierluigi Gambetti, MD, Mark Cohen, MD, and Uros Roessmann, MD. Since completing his neuropathology training, Dr. Castellani has held faculty positions at Case Western Reserve University, Michigan State University, and, most recently, the University of Maryland School of Medicine, where he is presently Professor of Pathology, Director of Neuropathology, Directory of Autopsy Services, and Director of the Pathology Graduate Program. Dr. Castellani is also the current President of the Maryland Society of Pathologists. Throughout his career Dr. Castellani has studied the pathology and pathogenesis of neurodegenerative disease, most notably human prion diseases and Alzheimer’s disease. His work in research years has focused on the role of Alzheimer’s disease pathological lesions, proteins and cascades comprising those lesions, upstream events including heavy metal toxicity and oxidative stress, and their relevance in clinical disease.

Importance of Published Article
Dr. Castellani’s paper, “Reexamining Alzheimer’s Disease: Evidence for a Protective Role for Amyloid-β Protein Precursor and Amyloid-β,” (J Alzheimers Dis 18, 447-452, 2009) is a synthesis of pathogenic hypotheses and their relationship with presumed causative lesions (e.g., amyloid-β) and molecules (amyloid-β, amyloid-β protein precursor). His assessment of the state of knowledge is a somewhat cynical and stinging rebuke (necessarily so in his view) of the major school of thought in Alzheimer’s disease pathogenesis, which he describes as reductionist and fundamentally backward. He bases this interpretation on the pathology, and the relationship between pathology and disease that clearly indicates plaques, amyloid-β protein precursor processing, and amyloid-β metabolism, as effect, or “host response,” rather than cause. He goes on to provide evidence for the beneficial and protective effects of amyloid formation across species, and its role as antioxidant, metal chelator, and oligomer detoxifier. Perhaps the most important contribution of this article overall is the previously unemphasized point that the pathology of chronic diseases in general, and Alzheimer’s disease in particular, tends to distract from upstream processes, and instead encourages the characterization and continued pursuit of small molecule cascades that are, at best, epiphenomenal.