A Sweet Solution for Alzheimer's Disease?

Certain variants of a simple sugar ameliorate Alzheimer's-like disease in mice, according to a new study by Canadian researchers. Although the new studies are still in the early stages, the findings could lead to new therapies that prevent or delay the onset of Alzheimer's disease.

The new studies show that some types of a sugar called cyclohexanehexol - also known as inositol - prevented the accumulation of amyloid ? deposits, a hallmark of Alzheimer's disease. Scyllo-inositol treatment also improved cognitive abilities in the mice and allowed them to live a normal lifetime. The study appeared in advance online publication of the journal Nature Medicine on June 11, 2006.

HHMI international research scholar and senior author Peter St George-Hyslop cautioned that the chemicals tested in these studies are not the type of inositol sold commercially as a nutritional supplement. That type - myo-inositol - has been shown previously to be ineffective at breaking up amyloid aggregates, he said.

In the brain of a person with Alzheimer's disease, small proteins called amyloid ? aggregate into plaques, and a protein called tau clumps into neurofibrillary tangles. The brain becomes inflamed and neurons atrophy and die. It's not completely clear what kind of amyloid ? peptide (monomers, oligomeric aggregates, or fibrillar aggregates) is responsible for the onset of disease, said St George-Hyslop of the University of Toronto. "Because we were able to show that scyllo-inositol specifically dispersed the high-molecular-weight oligomeric aggregates, this study confirms that the initiating event is the accumulation of oligomeric aggregates of amyloid ? peptide," he said.

Previous work by JoAnne McLaurin, also of the University of Toronto and lead author of the Nature Medicine paper, showed that several types of inositol could stop amyloid proteins from aggregating in test tubes. To see if these compounds could do the same in living animals, St George-Hyslop, McLaurin, and colleagues tested them in transgenic mice with human genes that predispose them to an Alzheimer's-like disease.

When the researchers treated these mice with scyllo-inositol, all of the animals' disease symptoms improved. Cognitive function was improved, amyloid plaques disappeared, inflammation declined, and the mice lived longer.

The scientists found that scyllo-inositol conferred these benefits not only if the mice were treated when they were very young and disease-free, but also if they were treated after the onset of disease.

As a model system, these mice "are pretty good, but they're not a perfect replica of the disease," St George-Hyslop said. The mice do not develop tau tangles, he explained, but they are prone to amyloid plaques, brain inflammation, cognitive disturbance, and early death, just like humans with Alzheimer's disease.

The researchers found that the scyllo-inositol worked better than the epi-inositol version. Scyllo-inositol produced more dramatic benefits overall, while epi-inositol worked only transiently and only when given before disease symptoms appeared.