Drug Found to Reverse the Ravages of Alzheimer's in Mice

american scientist ^ | March 01, 2006 | Kate Wong

[S0122017]

March 01, 2006

Drug Found to Reverse the Ravages of Alzheimer's in Mice

Researchers have identified a compound that could significantly improve treatment of Alzheimer's disease. When administered to mice engineered to develop hallmarks of the disease, the drug reversed cognitive decline and reduced the two types of brain lesions--plaques and tangles--that occur in Alzheimer's patients. Frank M. LaFerla of the University of California at Irvine and his colleagues gave Alzheimer's mice and normal mice daily doses of the drug, known as AF267B, for eight weeks and then tested their ability to learn to locate a hidden platform in a tank of water. Alzheimer's mice that received AF267B, they found, performed significantly better on this test than untreated mice did. And normal mice showed no ill effects from the drug. But in a second memory test, wherein the animals had to learn to associate a dark chamber with a mild electric shock, the treated Alzheimer's mice did not outperform their untreated counterparts. Subsequent analyses of the brains of these animals revealed that the drug reduced the plaques and tangles in the hippocampus, which is known to play a key role in learning the water maze, but not in the amygdala, which figures importantly in the dark chamber test.

AF267B seems to work in part by enhancing the activity of receptors for the neurotransmitter acetylcholine. The compound binds to these so-called M1 receptors, and in so doing boosts the levels of an enzyme called alpha secretase. This enzyme blocks the production of beta-amyloid proteins, the accumulation of which into plaques is theorized to lead to Alzheimer's. The amygdala, it turns out, does not produce much alpha secretase, and even with the help of AF267B could not make enough to block the formation of beta-amyloid. Hence, the mice's poor performance on the dark chamber task.

The study also suggests that AF267B reduces the activity of an enzyme known as GSK3beta, which in turn prevents so-called tau proteins from clumping together into the disease's signature tangles. The team additionally found that suppressing the M1 receptors with a drug called dicyclomine exacerbated learning and memory impairment in the Alzheimer's mice, and led to the appearance of more of the plaques and tangles. These results, the scientists say, underscore the important role of M1 receptors in modulating these hallmarks of Alzheimer's disease.

It remains to be seen whether AF267B is as effective in humans suffering from Alzheimer's as it is in the mice. But for their part, LaFerla and his collaborators are hopeful. "AF267B could be a tremendous step forward in the treatment of Alzheimer's disease," LaFerla observes. "Not only does it appear to work on the pathology of Alzheimer's and ease its symptoms, it crosses the blood-brain barrier, which means it does not have to be directly administered to the brain, a significant advantage for a pharmaceutical product. Although we cannot determine what the effects of AF267B will be in humans until clinical trials are complete, we are very excited by the results our study has yielded." The findings will be published tomorrow in the journal Neuron. --Kate Wong

[S0122017]

It actually seems to reverse the effect in mice.

[DocRock]

bttt

[Brett66]

I wonder if it improves memory in people without Alzheimer's?

[S0122017]

Probably not, healthy people have almost or no plaques.
If you want to improve memory you may be able to use ginkgo biloba. I myself found it does seem to improve memory a little bit. It also seems to make me feel far more rested after sleep, i think it is cause biloba increases blood flow to the (human) brain, and one sleep's functions is to repair the brain while it is on 'stand-by'.
I suspect increased blood flow might increase repair.

[Tax-chick]

then tested their ability to learn to locate a hidden platform in a tank of water

Did they teach the mice to swim? Genetically engineer them with gills? Fit them with tiny Scuba gear?

But seriously, this is very interesting news, and it would be great if something came of it in time to help my father.

[S0122017]

All mice can swim.

Most small critters that i know can, they just don't like it.

[Tax-chick]

All mice can swim.

Thanks! My new fact for the day :-).

[Yaelle]

I am sure that the fact that the mice were put into water was sufficient motivation for them to try and find the platform. Not a bad idea for an experiment. These lab animals do not die in vain. Alzheimers is such an awful disease to get; if they can help us find a cure, G-d bless those little creatures!!

[2 Kool 2 Be 4-Gotten]

Cool! I'll keep this in mind if I ever have a older pet mouse that can't remember where they put their car keys, or remember whether they left the oven on.