Michigan State University, BS, 1986
Wayne State University, MD, 1990
Wayne State University, Anatomical Pathology, 1990-1993
Case Western Reserve University, Neuropathology, 1993-1995
Research InterestsMy research is dedicated to the study of neurodegenerative disease pathogenesis, including Alzheimer’s disease and so-called prion diseases. We have extensively characterized sporadic Creutzfeldt-Jakob disease in terms of clinical phenotype, pathological alterations, prion chemistry, and molecular genetics, and have found that specific features of the PrPsc molecule are remarkable predictors of phenotype. Further, we have recently characterized a form of human prion disease characterized by “protease-sensitive PrPsc,” expanding the spectrum of disease and drawing even closer overlap with more common neurodegenerative diseases. My studies on Alzheimer’s disease relate to early events in disease progression; as such, we have found a number of adducts related to oxidative stress in vulnerable, but pathologically normal, neurons in Alzheimer’s disease, as well as in control brains several decades prior to the onset of neurodegeneration. Our findings have significant implications in terms of therapeutic intervention.
Castellani, R.J., Parchi, P., Stahl, J., Cohen, M., & Gambetti, P. Early biochemical and pathological changes in Creutzfeldt-Jakob disease: Study of brain biopsies. Neurology, 46:1690-1693, 1996.
Parchi, P., Castellani, R.J., Capellari, S., Ghetti, B., Young, K., Chen, S.G., Farlow, M., Dickson, D.W., Sima, A.A.F., Trojanowski, J.Q., Petersen, R.B., & Gambetti, P. Molecular basis of phenotypic variability in sporadic CJD. Annals of Neurology, 39:767-778, 1996.
Castellani, R.J. Multiple system atrophy: clues from inclusions. American Journal of Pathology, 153:671-676, 1998.
Castellani, R.J., Perry, G., Fox, P., Harris, P.L.R., & Smith, M.A. Is redox active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin? Free Radicals in Biology and Medicine, 26:508-512, 1999.
Castellani, R.J., Hirai, K., Aliev, G., Drew, K.L., Nunomura, A., Takeda, A., Cash, A.D., Obrenovich, M.E., Perry, G., & Smith, M.A. Perspective: Role of mitochondrial dysfunction in Alzheimer’s disease. Journal of Neuroscience Research, 70:357-360, 2002. Review
Castellani, R.J., Perry, G., Siedlak, S.L., Nunomura, A., Shimohama, S., Zhang, J., Montine, T., Sayre, L.M., & Smith, M.A. Hydroxynonenal adducts indicate a role for lipid peroxidation in neocortical and brainstem Lewy bodies in humans. Neuroscience Letters, 319:25-28, 2002.
Castellani, R.J. Variant Creutzfeldt-Jakob disease. An overview. Pathology Case Reviews, 9:16-19, 2004.
Castellani, R.J., Colucci, M., Xie, Z., Zou, W., Li, C., Parchi, P., Capellari, S., Pastore, M., Rahbar, M.H., Chen, S.G., & Gambetti, P. Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt-Jakob disease. Neurology, 63:436-442, 2004.
Cali I, Castellani R, Yuan J, Al-Shekhlee A, Cohen ML, Xiao X, Moleres FJ, Parchi P, Zou WQ, Gambetti P. Classification of sporadic Creutzfeldt-Jakob disease revisited. Brain. 2006 Sep;129(Pt 9):2266-77.
Castellani RJ, Lee HG, Zhu X, Nunomura A, Perry G, Smith MA. Neuropathology of Alzheimer disease: pathognomonic but not pathogenic. Acta Neuropathol (Berl). 2006 Apr 27; [Epub ahead of print]