What is the significance of the paper? "In the field of Alzheimer's disease, it is well known that a bad actor in the brain is a protein called APP, and what we found is a new twist on our understanding of what APP does.

APP is a large protein that sits in the cell membrane, and for many years the field has focused on a piece of the protein that's down here near the cell membrane — it's called Abeta.

It's been argued that Abeta is toxic and contributes to the degeneration that occurs in the disease. What we found is that a different portion of the APP molecule sitting up here, which we call N-APP, actually can trigger the death and degeneration of neurons, and we've figured out how it is that it triggers that degeneration — the mechanism through which it triggers that degeneration.

So we believe that this could be involved in either the initiating or helping the progression of Alzheimer's disease."

What are the potential therapeutic implications? "This new understanding provides us with a number of new therapeutic targets. We can try to prevent the initiation or progression of the disease by blocking the portion of the APP molecule that we've identified or some of the other downstream signaling mechanisms that we've pinpointed as well. It provides us with a whole host of new entry points to try to block or mitigate the effects of the disease."

How does this work fit into Genentech's wider efforts in neuroscience? "We're tackling a number of other neurological diseases apart from Alzheimer's: Parkinson's disease, ALS — also know as Lou Gehrig's disease — and Glaucoma, for example. And recently, we've started to expand beyond neurodegenerative diseases into other areas including spinal cord injury, pain and other psychiatric and affective disorders. So it's an important focus for us, but it's really just the beginning of a larger effort we're mounting."

Why did Genentech decide to move into neuroscience? "We think the time is right now because the unmet need is enormous in both neurological and psychiatric disease, and the science has been breaking open and accelerating over the past several years.

In addition, to tackle targets in the brain in most cases, we're going to have to use small molecules, and it's only in the past few years that we've built up our small molecule drug discovery organization to the point where we can actually do that.

In addition, perhaps it helps that Richard H. Scheller and I are both neuroscientists, so we follow this closely. We've been very fortunate to recruit Morgan Sheng as VP of neuroscience to help build out our efforts in that field."

How is Genentech's approach to neuroscience different? "We place a really big effort on understanding the basic biology of the mechanisms and diseases that we're studying, trying to add fresh insights and understand them in depth, not just try to make drugs against specific targets. This is the approach that we take in all of our therapeutic areas, of course, and neuroscience is no exception, but I think that makes us stand out from many other companies."