25 February 2010. Both baptists and tauists can celebrate this year’s annual Award for Medical Research in Alzheimer’s Disease, sponsored by the MetLife Foundation. Awards go to Eddie Koo, University of California, San Diego, and Todd Golde, University of Florida, Gainesville, for their work on modulators of -γ-secretase, the transmembrane protease that releases amyloid-β (Aβ) from its precursor. Equally recognized are Eva-Maria Mandelkow and Eckhard Mandelkow, Max-Planck-Institute for Structural Molecular Biology in Hamburg, Germany, for their pioneering work on the microtubule-binding protein tau. Aβ and tau are principal elements in amyloid plaques and neurofibrillary tangles, respectively, two pathological hallmarks of Alzheimer disease and fodder for the great baptist-tauist debate of previous years.
The MetLife Foundation has supported AD research since 1986 with over $12 million in research grants through its Awards for Medical Research in Alzheimer's Disease program. In addition, the MetLife annual award for AD research has become a prestigious one in the field and a milestone in many researchers’ careers. This year, each winner receives a check for $25,000 and a $100,000 grant to further his or her research.
Koo and Golde, former ARF Scientific Advisory Board (SAB) members and regular contributors to Alzforum, are recognized for discovering that some non-steroidal anti-inflammatory drugs (NSAIDs) have unexpected effects on γ-secretase, nudging the enzyme so that it snips slightly smaller Aβ peptides from the precursor protein (see ARF related news story). The work was carried out while Golde was at the Mayo Clinic in Jacksonville, Florida. Their finding was significant because longer (42-amino-acid) Aβ peptides are more likely to form toxic oligomers and amyloid plaques and because the NSAIDs did not seem to interfere with γ-secretase trims of other transmembrane proteins, including Notch. Blocking Notch cleavage can cause potentially severe adverse effects. Since Koo and Golde’s original discovery, many academic and pharmaceutical labs have pursued γ-secretase modulators that limit production of Aβ42 while sparing cleavage of other essential membrane proteins. Such compounds have entered, or are close to entering, clinical trials, though an early one has since failed in Phase 3 (see ARF related news story).
The Mandelkows are honored for an impressive body of research that ranges from work on tau protein structure and aggregation (see ARF related news story), to mouse models of tauopathies (see ARF related news story), to preclinical drug development. Amongst their achievements, the Mandelkows promoted the idea that tau, which binds the microtubules along which intracellular cargo travels, can block transport of essential components down long neuronal axons, and that knocking tau off those microtubules by phosphorylation may be the cells’ response to stress (see ARF related news story).
This year's awards are presented today at the St. Regis Hotel in Washington, D.C.—Tom Fagan.