2008 Awardee
Milan Fiala, M.D.

Milan Fiala, M.D., a Research Professor of Orthopaedic Surgery at UCLA, Los Angeles, California, received his initial training at the University of Charles IV, Prague, Czechoslovakia and his M.D. degree at the University of Geneva, Switzerland. He obtained a M.Sc. (Epidemiology) from Harvard School of Public Health and pursued translational research in respiratory, herpes and retroviruses viruses at the University of Washington, the University of Pennsylvania and UCLA, where his work played key role in controlling infections of immunocompromised patients.  In the last decade he has developed a modification of the amyloid-beta hypothesis suggesting that the underlying problem of patients with Alzheimer's disease lies in the defectiveness of the innate immune system to clear amyloid-beta in the brain. Dr. Fiala’s laboratory is situated in Orthopaedic Hospital Research Center and includes key UCLA collaborators, John Adams, M.D., Martin Hewison, Ph.D., Philip T. Liu, Ph.D., Araceli Espinosa-Jeffrey, Ph.D., Mark J. Rosenthal, M.D., John M. Ringman, M.D., and research staff including many gifted students. Outside collaborators include John Cashman, Ph.D., HBRI, San Diego; Naoyuki Taniguchi, Osaka University; and Albert S. Lossinsky, New Jersey Neuroscience Institute, Edison, New Jersey.

Importance of Published Article
The work presented in the paper, "Phagocytosis of amyloid-beta and inflammation: two faces of innate immunity in Alzheimer’s disease" (J Alzheimers Dis 11: 1-7, 2007), is a review and a new concept of Alzheimer's disease. The solid data behind the new concept were previously published and showed: a) infiltration of Alzheimer's disease brain by macrophages (Eur J Clin Invest 32:360, 2002); b) irregular clearance of amyloid-beta in plaques (J Alzheimers Dis 7:221-232, 2005); c) enhanced clearance of amyloid-beta by treatment of immune cells with curcuminoids (J Alzheimers Dis 10: 1-7, 2006); and d) defective transcription of genes important for phagocytosis by macrophages of patients (Proc Natl Acad Sci USA 104: 12849-12854, 2007). The basic concept is that physiological balance between phagocytosis and degradation of amyloid-beta and inflammation maintain the pristine condition of neurons. However, in patients with Alzheimer's disease, phagocytosis, degradation of amyloid-beta, and clearance of neurons decrease and inflammation increases due to transcriptional imbalance. In fact, in vitro in brain sections normal macrophages search for neurons (due to a chemokine in neurons), infiltrate and clear neurons of oligomeric and soluble amyloid-beta, whereas macrophages of patients are defective in these functions. However, natural substances, such as curcuminoids, may restore this balance by increasing the transcription of key genes, including Toll-like receptors. Ongoing work based on these concepts will further expand these ideas to develop a blood test for early detection of immune deficiency leading to Alzheimer's disease. It is hoped that these discoveries will lead to all-inclusive approach to Alzheimer's disease:  detection at an early stage and prevention by curcuminoids and other substances, which are likely to be effective before neuronal demise occurs.