22 May 2014

Mathias Jucker, Lary Walker, and Riqiang Yan share this year's MetLife Foundation Award in Medical Research. Jucker, from the University of Tubingen, Germany, and Walker, from Emory University, Atlanta, were recognized for their studies on the spread of toxic proteins in the brain, and how that insidious crawl contributes to the progression of Alzheimer's and other neurodegenerative diseases. Yan was honored for his role in the discovery of β-secretase, the enzyme that helps snip Aβ from its precursor. Jie Shen, Brigham and Women's Hospital, Boston, received the Promising Research in Alzheimer’s Disease Award for her work on the function of presenilin, the catalytic component of the γ-secretase complex that generates Aβ. 

Yan independently identified β-secretase, or BACE, as a membrane-bound aspartyl protease (Yan et al., 1999). Other reports identifying BACE came out at about the same time, including one by Robert Vassar at Northwestern University in Chicago, who shared the MetLife prize in 2008. In subsequent studies, Yan found that knocking out BACE leaves mice prone to seizures and neurodegeneration, a warning sign to those developing BACE inhibitors as potential therapeutics for AD (see Jul 2010 news story). 

By injecting minuscule aggregates of Aβ into the brains of mice, Jucker and Walker discovered that misfolded pathogenic forms of the peptide act as seeds to promote the appearance of new aggregates (see Walker et al., 2002; May 2004 conference story; Alzforum Webinar). Their work cemented the idea that different forms, or strains, of Aβ can propagate in the brain, hinting that the peptide has prion-like properties (see Sep 2006 news story on Meyer-Luehmann et al., 2006). Researchers have since reported that tau, α-synuclein, and other toxic proteins behave in a similar fashion.

Shen showed that knocking out presenilin-1 reduces Aβ production in mice, initially supporting the idea that γ-secretase might be a valuable therapeutic target (see Sep 2001 news story; Jul 2005 news story). Subsequent research revealed properties of presenilins beyond generation of Aβ, however, fanning debate about whether familial AD mutations in the PS genes cause a loss of function that disturbs neurotransmission and in this way promotes neurodegeneration (see Apr 2004 news story; Aug 2009 news story). 

The awards were presented at a ceremony in New York on May 15. Yan received a $200,000 institutional grant and a $50,000 personal prize. Jucker and Walker shared the same. Shen received a $100,000 institutional grant.—Tom Fagan