2011 Awardee
Mark A. Smith, Ph.D.

Mark A. Smith received his Ph.D. in 1990 from Nottingham University. In 1992, he joined the laboratory of George Perry at Case Western Reserve University, where he provided the first solid foundation to establish the role of oxidative stress in Alzheimer disease. His body of work on this topic and his dedication as a teacher and willingness to serve the university in many capacities earned him the title Professor in 2002. His work on cell cycle re-entry, free radical involvement and mitochondrial disruption led to numerous honors such as the Jordi-Folch award from the American Neurochemistry Society, Hermann-Esterbauer Award from the HNE Society, the Outstanding Investigator Award from the American Society for Investigative Pathology, Denham Harman Research Award from the American Aging Association, and the Goudie Lecture and Medal from the Pathological Society of Great Britain and Ireland. Together with his first Ph.D. student Xiongwei Zhu, he developed the two-hit hypothesis of Alzheimer disease and is perhaps most known in the field for arguing against the amyloid hypothesis. Even more, he is known as being an exceptionally generous mentor and colleague (http://neurotree.org/neurotree/peopleinfo.php?pid=9563). Sadly, his life was cut tragically short in December 2010, however his work continues on, and his memory will never be forgotten by those whose lives he touched. Please visit http://www.j-alz.com/marksmith.html for more details of his life and comments from those whose lives' he touched.

Importance of Published Article
Dr. Smith’s paper, “Increased Iron and Free Radical Generation in Preclinical Alzheimer Disease and Mild Cognitive Impairment” (J Alzheimers Dis 19, 363-372, 2010), documents how the accumulation of redox active iron is correlated with the earliest stages of cognitive impairment. While increased iron and iron related compounds have been long associated with the pathological structures amyloid plaques and neurofibrillary tangles found in advanced Alzheimer disease, the finding of increased iron in the brains of preclinical patients suggests a great role for this potent source of free radicals in early disease development. Importantly, redox active iron was not only found to be a feature of the cortical regions, but the iron dyshomeostasis was mirrored in the cerebellum. More often than not, the cerebellum is regarded as an “unaffected” brain region, however, this study clearly finds that free radical attack is a global brain event. From this work, treatment avenues, imaging techniques, and concepts of disease progression and brain region involvement will be revolutionized.