Brain imaging changes in individuals with Down symdrome, may help advance Alzheimer trials

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Apr 14, 2015

Researchers have characterized 3 different brain imaging changes in individuals with Down syndrome, who are at very high risk for development of Alzheimer disease, even before the onset of progressive memory and thinking problems. Their findings could help set the stage to evaluate promising treatments to slow down or prevent the onset of Alzheimer symptoms in these individuals, according to a study published in Alzheimer's & Dementia.

The scientists at Banner Sun Health Research Institute (BSHRI) and Banner Alzheimer's Institute (BAI) have also identified the approximate age—about 35 to 40 years—at which Alzheimer-associated brain imaging changes occur in the Down syndrome population, which could help pinpoint when to initiate investigational treatments in those trials.

Almost 80% of Down syndrome individuals will develop Alzheimer disease, due partly to improved medical care that has led people with Down syndrome to live longer and develop Alzheimer-related brain changes. Down syndrome is caused when people have 3 copies of the 21st chromosome, which carries a gene for the amyloid precursor protein (APP). This results in over-expression of APP, leading to the overproduction of amyloid, a protein linked to Alzheimer disease, the deposition of amyloid plaques, and the development of memory and thinking problems at relatively young ages.

"The number of people with Down syndrome who go on to Alzheimer's symptoms has tripled in the last twenty years," said Marwan Sabbagh, the study's lead researcher and director of BSHRI. "There is a growing need to find interventions to treat and prevent Alzheimer's in these individuals, and there is an opportunity to do so in a way that could help find effective Alzheimer's prevention therapies for everyone."

Sabbagh and his team used PET imaging to detect the accumulation of beta-amyloid, as well as a pattern of reduced brain activity that is characteristic of Alzheimer disease. In addition, MRI scans were used to measure gray matter volume in 3 types of study participants: 5 participants with Down syndrome who already demonstrate clinical features of Alzheimer disease, 12 participants with Down syndrome who have not yet shown clinical evidence of Alzheimer disease, and 9 healthy participants who did not have either Down syndrome or Alzheimer disease.

"We and other researchers have been interested in detecting and tracking Alzheimer's, starting before the onset of cognitive impairment in individuals at genetic risk for the disease," said Eric Reiman MD, executive director of BAI, a leader of the Alzheimer's Prevention Initiative (API), and senior researcher for this study. "We have used this approach to help launch Alzheimer's prevention trials in people with other genetic risk factors, and we hope that the same approach can help empower people with Down syndrome in the fight against this disease."

Comparing the 3 groups, researchers found that the Down syndrome with Alzheimer disease group had significantly higher accumulation of beta-amyloid, lower brain activity in brain regions known to be affected by Alzheimer disease, and smaller gray matter volumes than the other 2 groups.

In comparing measurements between the group with Down syndrome without Alzheimer dementia and the healthy volunteer group, researchers also found more accumulation of amyloid protein in the Down syndrome participants, even though these participants were not yet exhibiting Alzheimer symptoms. This finding is consistent with previous evidence showing that amyloid deposition precedes clinical symptoms of Alzheimer disease.

The findings led Sabbagh and his team to conclude that amyloid deposition begins around 35 to 40 years of age, before the onset of progressive memory and thinking problems.

The research team has received financial support to determine how these and other brain imaging and cognitive features of Alzheimer disease change over time in people with Down syndrome, information that will help inform the design of future prevention trials in this population.

Source: News Release
GYMR
April 14, 2015

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