BioCentury
ARTICLE | Tools & Techniques

Untangling the Alzheimer's targets

February 26, 2001 8:00 AM UTC

A number of pharma and biotech companies are targeting beta and gamma secretases as a way to prevent production of amyloid-beta, the neurotoxic peptide that forms extracellular aggregates called amyloid plaques found in the brains of Alzheimer's patients. Now evidence from a knockout mouse indicates that beta secretase is the principal protease responsible for formation of amyloid-beta. Indeed, the work shows that this target may be even better than previously thought, since mice missing the BACE1 gene that codes for beta secretase appear healthy and normal.

Amgen Inc. (AMGN, Thousand Oaks, Calif.) this week published inNature Neuroscience that a transgenic mouse with the protease gene BACE1 knocked out seems to be normal, suggesting that inhibiting this enzyme would not cause adverse effects. The finding is somewhat surprising, because BACE1 is present throughout the body and is expressed at high levels in the brain and pancreas. But the non-pathologic function of the gene is not yet known...