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Research Grants - 2005


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Research Grants 2005


To view an abstract, select an author from the vertical list on the left side.

2005 Grant - Weiner

Antibody -Independent Clearance of Beta-Amyloid in a Mouse Model of Alzheimer's Disease

Howard L. Weiner, M.D.
Brigham and Women's Hospital
Boston, Massachusetts

2005 Investigator-Initiated Research Grant

Beta-amyloid is a protein fragment that may be a key toxic factor in Alzheimer's disease. A large effort in drug development studies is to find a treatment that clears beta-amyloid from the brain. The first clinical studies of an Alzheimer "vaccine" used a modified beta-amyloid molecule intended to induce the immune system to develop an antibody to beta-amyloid. An antibody would then "hunt down and attack" beta-amyloid in the brain.

Unfortunately, this treatment caused unwanted and severe inflammation in some of the participants. Nonetheless, this study also showed that the activa-tion of certain immune-system scavengers may be a key mechanism for beta-amyloid clearance.

Howard L. Weiner, M.D., and colleagues unexpectedly observed that a variant form of a multiple sclerosis drug cleared beta-amyloid in mice. This clearance occurred even though there was no antibody to beta-amyloid and apparently because of the activation of immune-system scavengers.

In this investigation, the researchers will assess whether this treatment prevents the accumulation of beta-amyloid in genetically altered mice that develop an Alzheimer-like disorder and whether the treatment prevents deficits in memory and learning skills. They will also determine whether the treatment has any toxic effect on the brain. Finally, they will study and characterize the mechanisms by which the treatment activates immune-system scavengers and beta-amyloid clearance. The outcome of this work may demonstrate a potential benefit of an approved drug to Alzheimer's disease.