Amyloid-beta peptide plaques (orange) in brain tissue are cleared by the sugar alcohol inositol.

Sugar might be bad for your teeth and waistline, but some sugars just might be good for your brain.

A research team led by HHMI international research scholar Peter St George-Hyslop of the University of Toronto has discovered that certain forms of the sugar alcohol inositol may rid the brain of amyloid beta plaques implicated in Alzheimer's disease.

Alzheimer's is literally a sticky problem, in which small proteins, called amyloid beta, adhere to each other to form plaques in the brain. These masses cause the choking and death of neurons, resulting in behavioral changes and—Alzheimer's most notable symptom—memory loss.

The group screened various compounds for their potential to unclog these clumps and ultimately chose inositol, which is present at the tips of certain cell-membrane molecules. Like many sugars, inositol has a ring-like structure. It also contains groups of paired hydrogen and oxygen molecules, typical of alcohols, which contort the structure into several distinct conformations called isomers.

St George-Hyslop and colleagues combined different inositol isomers with amyloid beta. Those that kept the sticky protein from clumping they fed to mice engineered to have Alzheimer's-like disease; the mice were given the isomers either before or after the onset of symptoms. Regardless of when it was administered, one isomer—scyllo-inositol—produced substantial improvements: reduction and prevention of plaque formation and increased cognitive function and longevity. Two other isomers were less effective: epi-inositol worked transiently only when it was used before the disease's progression; myo-inositol, found in supplements in nutritional stores, had no effect.

The team's research appeared in the July 2006 issue of Nature Medicine. The results, according to St George-Hyslop, are the final missing element in the evidence that amyloid beta plaques play a key role in causing Alzheimer's disease.

Because scyllo-inositol is already present in humans and can cross the blood-brain barrier to reach the brain, it holds therapeutic promise. Transition Therapeutics, Inc. (Toronto, Ontario) in which St George-Hyslop has a small financial interest, is already performing human clinical trials with the compound.

Photo: Courtesy of St George-Hyslop Lab