Friday, December 17, 2010

Alzheimer's researchers get closer to understanding the disease

The intro to a longer story in The NY Times Science section:

Alzheimer’s researchers are obsessed with a small, sticky protein fragment, beta amyloid (pictured), that clumps into barnacle-like balls in the brains of patients with this degenerative neurological disease.

It is a normal protein. Everyone’s brain makes it. But the problem in Alzheimer’s is that it starts to accumulate into balls — plaques. The first sign the disease is developing — before there are any symptoms — is a buildup of amyloid. And for years, it seemed, the problem in Alzheimer’s was that brain cells were making too much of it.

But now, a surprising new study has found that that view appears to be wrong. It turns out that most people with Alzheimer’s seem to make perfectly normal amounts of amyloid. They just can’t get rid of it. It’s like an overflowing sink caused by a clogged drain instead of a faucet that does not turn off.

That discovery is part of a wave of unexpected findings that are enriching scientists’ views of the genesis of Alzheimer’s disease. In some cases, like the story of amyloid disposal, the work points to new ways to understand and attack the disease. If researchers could find a way to speed up disposal, perhaps they could slow down or halt the disease. Researchers have also found that amyloid, in its normal small amounts, seems to have a purpose in the brain — it may be acting like a circuit breaker to prevent nerve firing from getting out of control. But too much amyloid can shut down nerves, eventually leading to cell death. That means that if amyloid levels were reduced early in the disease, when excess amyloid is stunning nerve cells but has not yet killed them, the damage might be reversed.

Yet another line of research involves the brain’s default network: a system of cells that is always turned on at some level. It includes the hippocampus, the brain’s memory center, but also other areas, and is the brain’s mind-wandering mode — the part that is active when, for instance, you’re driving in your car and you start thinking about what you will make for dinner. That brain system, scientists find, is exactly the network that is attacked by Alzheimer’s, and protecting it in some way might help keep the brain healthier longer.

For example, during non-dreaming sleep, the default network is thought to be less active, like a light bulb that has been dimmed. The network also ramps down during intense and focused intellectual activity, which uses different areas of the brain. One emerging theory suggests that if the default network can be rested, amyloid production might be decreased, allowing even an amyloid disposal system that was partly hobbled by Alzheimer’s to do a better job.

The result of all this work is a renewed vigor in the field. After years in which it was not clear how to attack this devastating disease, scientists have almost an embarrassment of riches. The research is in early stages, of course, and there are many questions about which discoveries and insights will lead to prevention or a treatment that works.

But there is a new hopefulness that, at long last, this terrible disease may eventually be conquered, said Richard Mohs, Alzheimer’s group team leader at Eli Lilly.

“We are much closer and quite optimistic that we will be able to do it,” Dr. Mohs said.