A recent study conducted on Down syndrome patients who died with Alzheimer's disease, shows that the earliest related brain changes may be seen in childhood. These findings indicate that anti-oxidants could be used to help prevent or slow the development of the disease. The study from the University of California, Irvine, College of Medicine, appears in the November issue of Neurobiology of Disease.

Research lead by Dr. Ira Lott, professor of pediatrics and neurology, and Elizabeth Head, research scientist at UCI's Institute of Brain Aging and Dementia, found that an oxidized version of a key protein linked to Alzheimer's disease was found in the brains of young deceased patients with Down syndrome. The levels of this oxidized form of the protein, called beta-amyloid, appear simultaneously with the early development of dementia seen in people with Down syndrome.

The findings extend the results of previous studies that observed inflammation in the brains of deceased Down syndrome patients who had already developed Alzheimer's disease. This study indicates that some of the earliest stages of Alzheimer's involve oxidative damage in the brain and points to anti-oxidants as a possible method of preventing or slowing the disease, both in Down syndrome and the general aging population.

In addition, a longer precursor protein that eventually forms beta-amyloid plaque is found at triple the levels in normal brains of people with Down syndrome. As a result, children with Down syndrome show some of the brain changes of Alzheimer as early as age 12; nearly all Down syndrome patients have evidence of Alzheimer’s brain changes of by age 40. Despite this, not all individuals with Down syndrome develop symptoms of the disorder. One of the mysteries of this condition is why some people with Down syndrome become ill with Alzheimer's disease and others survive to older ages with no change in their mental functioning.

"Because individuals with Down syndrome develop the brain changes of Alzheimer's disease at such an early age, they can show us the very beginning stages of the condition," Lott said. "Not only is this valuable for determining possible ways to keep so many people with Down syndrome from getting Alzheimer's disease, it may help us find better ways to prevent and treat Alzheimer's disease in general."

The researchers found the oxidized form of the beta-amyloid protein in deceased Down syndrome patients who had died in their 30s. This is much younger than patients with only Alzheimer's, who had an average age of 76 years old in the study. This oxidized form was found in the frontal lobes of the brain, an area associated with behavioral changes seen in Alzheimer's and other dementias.

Since the patients were young when they showed signs of dementia, the researchers were able to track the growth and development of the plaques and beta-amyloid as Alzheimer's progressed, providing the first look at the earliest stages of the disease. Only half of the very first beta-amyloid proteins to appear were oxidized, but as the proteins--and the patients--became older, the rate of oxidation rose sharply. By age 40 and older, the beta-amyloid and plaques resembled levels seen in much older patients who had Alzheimer's but who did not have Down syndrome. The oxidized form of beta-amyloid was rarely observed in elderly people who did not have symptoms of Alzheimer's or other dementias.

Earlier studies by Head, Lott and their co-workers had found evidence of inflammation in the brains in Down syndrome patients who were about 40 years old. The researchers suggest that the early stages of oxidation constitute the first reaction of the body to the newly formed beta-amyloid and plaques and the first steps to dementia seen in Alzheimer's disease.

"The oxidation process continues to rise and may lead eventually to inflammation responses in the brain, which, in turn, increases the severity of dementia in all patients, not just those with Down syndrome," Head said. "This suggests that the appropriate anti-oxidant therapy, given at the right time, may be able to prevent what was an inevitable case of Alzheimer's in patients with Down syndrome. It may also provide us with a new, effective way to prevent, and perhaps treat, Alzheimer's disease."

The researchers are now focusing on determining what anti-oxidant therapy may be effective and how such therapy may affect the disease at its various stages. They are also mapping out the progression of Alzheimer's, to further determine how it progresses.