Alzheimer Disease (AD) is characterized by hallmark lesions called amyloid plaques in the brain. The plaques are formed by the aggregation of small peptides (proteins), called amyloid beta peptide (Abeta), that are produced when a larger protein called amyloid precursor protein (APP) is cleaved by the action of two enzymes, beta-APP cleaving enzyme and gamma-secretase. Many scientists are developing inhibitors of these enzymes as possible therapies. In the meantime, other researchers are trying to test whether and how such approaches might work, at least in principle. Joanna Jankowsky, David Borchelt, and colleagues from institutes across the country, including Johns Hopkins School of Medicine, the Mayo Clinic Jacksonville, the National Cancer Institute, University of Florida, and the California Institute of Technology have some answers.
As they report in the international open-access medical journal PLoS Medicine, they have engineered mice to continuously produce Abeta in their brains. The production can be switched off by giving the mice the antibiotic tetracycline in their drinking water. This switch-off at a certain point is similar to what would happen to human patients who would receive enzyme inhibitors once diagnosed with AD. Without tetracycline, the brains of the mice at six months of age are loaded with amyloid plaques. When the researchers switched the system off after some initial plaques had formed, they found two things: the existing plaques didn't grow or spread to other areas of the brain, but they did not go away either.
As always, results from animal models cannot simply be extrapolated to human disease. However, this study suggests that treatment with drugs that lower production of Abeta can prevent progression of AD but not reverse the disease. While overall encouraging, the results emphasize the importance of early treatment with drugs that inhibit Abeta production.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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