UCI part of US effort to find Alzheimer's biomarkers in people with Down syndrome

A University of California, Irvine research team is part of a $37 million national effort to identify biomarkers that will predict the onset of Alzheimer's disease in people with Down syndrome.

UCI pediatric neurologist Dr. Ira Lott and colleagues will receive $4.7 million of that funding from the National Institute on Aging to support his continuing work to uncover the mystery of progressive cognitive impairment seen in some people over 40 with Down syndrome. Lott is a pioneer and a leader in neurological research on Down syndrome.

"Along with identifying the pre-existing factors for Alzheimer's disease, the ultimate goal of the research is to identify the susceptibility to dementia in time for treatment interventions to prevent dementia in Down syndrome," he said. "Once dementia has begun, virtually all studies, including our own, indicate that it's too late. We wish to afford people with Down syndrome the same opportunities for intervention as those in the general population."

The link between Alzheimer's and Down syndrome is well-known. People with Down syndrome are born with an extra copy of chromosome 21, which contains the amyloid precursor protein gene. This gene plays a role in the production of harmful amyloid plaque, sticky clumps that build up outside neurons in Alzheimer's disease. Having three copies of this gene is a known risk factor for early-onset Alzheimer's in middle-aged people.

The National Institutes of Health's Biomarkers of Alzheimer's Disease in Adults with Down Syndrome Initiative establishes funding for two research teams that will pool data and standardize procedures, increase sample size, and collectively analyze data that will be made widely available to the research community. The teams will employ an array of biomarkers to identify and monitor Alzheimer's-related brain and cognition changes in Down syndrome volunteers 25 and older. The measures include:

For the first time in people with Down syndrome, positron emission tomography brain scans to detect tau, the twisted knots of protein within brain cells that are a hallmark of Alzheimer's disease; PET scans that track brain volume and function, levels of amyloid and glucose (energy used by brain cells), and quantities of amyloid and tau in cerebrospinal fluid and blood; Blood tests to identify biomarkers in blood, including proteins, lipids and indicators of inflammation; Blood tests to collect DNA for genome-wide association studies identifying the genetic factors that may increase the risk of - or protect against - developing Alzheimer's; and Evaluations of medical conditions and cognitive and memory tests to determine levels of function and monitor any changes.

Aside from earlier onset, Alzheimer's in people with Down syndrome is similar to Alzheimer's in others. The first symptom may be memory loss, although people with Down syndrome also tend to exhibit behavioral differences and problems with walking.

"However, even with advancing age, not all people with Down syndrome actually develop dementia," Lott said. "The purpose of the research is to determine which biomarkers may best predict cognitive decline."

His team is part of a group that includes investigators from the Columbia University Medical Center in New York City; the Kennedy Krieger Institute/Johns Hopkins University in Baltimore; Massachusetts General Hospital/Harvard University in Boston; and the University of North Texas Health Science Center in Fort Worth.

Lott said his team will study up to 100 participants at UCI's Brain Imaging Center and the Institute for Clinical & Translational Science research clinics in Hewitt Hall on campus and at the UC Irvine Medical Center.

Provided by University of California, Irvine