Eduardo M. Castaño

Fellow: Awarded 2011

Field of Study: Medicine and Health

Competition: Latin America & Caribbean

Eduardo M. Castaño is one of the world’s leading researchers on the pathophysiology of Alzheimer’s disease (AD). Among the principal focuses of his work are the relationship of amyloid peptides, specifically beta amyloid (Aβ), to the neuronal degeneration associated with AD and the development of anti-Aβ immunotherapy.

Dr. Castaño received his medical degree, with honors, from the University of Buenos Aires in 1980, and on completion of his residency in internal medicine at the Hospital de Clínicas José de San Martín (UBA’s teaching hospital) he was appointed its Chief Resident in internal medicine (1984-85). Then, driven by a growing interest in the mechanisms of autoimmune diseases, he applied for and received a postdoctoral fellowship to develop his skills as a medical researcher in the lab of Blas Frangione at New York University.

While working in Dr. Frangione’s lab (1986-88) he was directly involved in two major breakthroughs: the demonstration that synthetic peptides could be used to mimic the Aβ obtained from the brains of Alzheimer and Down Syndrome patients; and the characterization of the first mutation in the amyloid precursor protein (APP) gene within the Aβ sequence that caused hereditary stroke in families of Dutch origin. Dr. Castaño was the lead author of “In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer’s disease β-protein,” a paper on some of the Frangione lab’s findings. It was published in Biochemical and Biophysical Research Communications (1986) and was selected as a “Milestone Paper” by the Alzheimer Research Forum.

After spending a few years in Buenos Aires to begin the process of establishing his own laboratory, he returned to NYU in 1992 as a Research Assistant Professor in the Department of Pathology, once again working with Blas Frangione. At that time Dr. Frangione had been given a Leadership and Excellence in Alzheimer’s Disease (LEAD) Award to support his further studies in this area. Placed in sole charge of the section of the LEAD-funded study dealing with the mechanisms of amyloid formation, Dr. Castaño produced fifteen papers detailing his group’s findings, including particularly significant ones on the interaction of amyloid proteins with apolipoprotein E published in such high-impact journals as The Journal of Biological Chemistry (1995) and Laboratory Investigation (1995). Concurrently, Dr. Castaño himself was given a grant from NYU’s Alzheimer Disease Core Grant Committee, which funded his team’s research on an Argentine family beset with early onset AD, which led to the discovery of a novel mutation in the presenilin 1 gene.

Although NYU offered him an assistant professorship in 1996, Dr. Castaño chose to return to Argentina, where, in spite of a lack of governmental funding and other obstacles, he secured a position as an Independent Researcher in the University of Buenos Aires and established a lab in its Faculty of Pharmacy and Biochemistry. Even after he was appointed an Independent Investigator with CONICET in 2002, he maintained his ties with UBA as an ad honorem Assistant Professor there (2002-07) and since then as an Invited Professor, lecturing on biological chemistry.

Dr. Castaño and his lab have made great strides in AD research. Among their most important advances are their detailing of the basic biochemical mechanisms of amyloid peptides degradation by the insulin-degrading enzyme (IDE), the abnormalities of this protease found in the brains of AD patients, and their solving in part the subcellular localization of this protease and its sorting mechanisms within cells. He is particularly gratified that his researches have spurred other labs around the world to begin investigating this neglected area of study. This work was supported in large part by Argentina’s Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) and an Initiated Investigator Grant from the Alzheimer’s Association (2003-06); the latter was a particular honor since it is rarely awarded to Latin American researchers.

In 2005, Dr. Castaño won appointment as Head of Laboratory at the Fundación Instituto Leloir (FIL), the premier scientific research facility in Argentina, in a competition for that position that attracted researchers from around the world. Soon afterwards he was appointed to FIL’s board of directors and was named Vice President of INIS Biotech, the division of FIL that develops and markets the applications of its researchers’ advances. At about that same time CONICET appointed him Vice Director of the Instituto de Investigaciones Bioquímicas de Buenos Aires; more recently he has become a member of CONICET’s medical sciences advisory board.

In addition to those administrative and advisory responsibilities, his continued research on IDE and other amyloid-proteases, and his sharing of his findings in dozens of articles in top-flight, refereed journals, he and his group have launched a collaborative research project with Dr. Alex E. Roher of Banner Sun Health Research Institute in Sun City, Arizona, on the biochemical composition of amyloid from transgenic mouse models of AD and from the brains of patients treated with anti-Aβ immunotherapy, and on potential cerebrospinal fluid biomarkers for sporadic Alzheimer’s disease. During his Guggenheim Fellowship term, he will be using Drosophila models to study the genetic basis of the neuronal vulnerability to amyloid peptides associated with dementias.