People With Down Syndrome Are Pioneers In Alzheimer's Research

by Jon Hamilton from NPR:
When researchers at the University of California, San Diego wanted to study an experimental Alzheimer's drug last year, they sought help from an unlikely group: people with Down syndrome.
"I had a CAT scan on my head, and I was in a special machine. It's called an MRI," says Justin McCowan, 39, whose parents drove him 125 miles from Santa Monica so he could participate in the study. McCowan also took brain function tests and spent hours with a needle in his arm so researchers could monitor levels of certain chemicals in his blood.
Alzheimer's researchers are increasingly interested in people like McCowan because "people with Down syndrome represent the world's largest population of individuals predisposed to getting Alzheimer's disease," says Michael Rafii, director of the Memory Disorders Clinic at UCSD.
Down syndrome is a genetic disorder that's best known for causing intellectual disability. But it also causes Alzheimer's. "By the age of 40, 100 percent of all individuals with Down syndrome have the pathology of Alzheimer's in their brain," Rafii says.
Down syndrome is caused by the presence of an extra copy of chromosome 21. And one of the genes on chromosome 21 happens to control the production of amyloid, the substance that forms the sticky plaques associated with Alzheimer's.
Because their bodies produce extra amyloid, most people with Down syndrome develop problems with thinking and memory by the time they reach 60. Rafii has chronicled the decline of one of his patients, a woman named Irma, by collecting her signatures from medical forms over the years.
The first one is from 1999, when Irma was in her mid-50s. "You can see her signature is on the line, it's clear, she wrote it in script," Rafii says. By 2005, though, she has switched to large block letters. By 2009, Irma is misspelling her name. By 2011, "there are only a few characters written that resemble letters," Rafii says. "And in the very last year it's completely blank."
People like Irma used to be rare because the medical problems associated with Down syndrome meant they rarely lived long enough to get dementia. Today, though, better medical treatments mean people with the disorder often live into their 60s.
And that has created a huge opportunity for Alzheimer's research, says William Mobley, chairman of the neuroscience department at UCSD. "This is the one group in the world that you could argue would benefit most by the institution of early therapy," he says.
Early therapy means starting people on drug treatment years before the symptoms of Alzheimer's appear. The approach has been hard to test because, in the general population, there's no good way to know who is going to develop Alzheimer's. But for people with Down syndrome, it's a near certainty.
Finding a drug that prevents Alzheimer's in people with Down syndrome could help millions of people who don't have the disorder, Mobley says. "This approach to treating Alzheimer's disease might apply to all of us," he says. "Imagine someday a drug that we all start taking when we're 25 so we never get Alzheimer's disease."
That's a long-term goal. But already, people with Down syndrome are making a difference in Alzheimer's research. Early work with Down patients helped confirm the importance of amyloid. More recently, people with the disorder helped test an eye exam that may offer a simple way to screen for Alzheimer's.
And then there's the study that Justin McCowan signed up for. It involves a drug from Transition Therapeutics called ELND005 that, in mice, can prevent the brain changes associated with Alzheimer's. Scientists hope the drug can do the same thing in people, including those with Down syndrome.
McCowan says he volunteered for the study because he wants to help other people, especially a friend of his named Maria, who also has Down syndrome. "I feel very sad about Maria because she doesn't remember anything," McCowan says.
His parents, Don and Annamarie McCowan, say their son's memory is still sharp. They hope that what scientists are learning from people like Justin will keep it that way.

UC San Diego Launches Unprecedented Down Syndrome Study

from UC San Diego:
To many, Down syndrome (DS) is a childhood condition. But improved health care means that individuals with DS now routinely reach age 50 or 60 years of age, sometimes beyond.  However, if they live long enough, people with Down syndrome are almost certain to develop Alzheimer’s disease (AD).
Risk estimates vary, but the National Down Syndrome Society says that nearly 25 percent of individuals with DS over the age of 35 show signs of Alzheimer’s-type dementia, a percentage that dramatically increases with age. Almost all develop dementia by the age of 60.
“The more we learn about Down syndrome and Alzheimer’s disease, the more we realize these conditions – one seen at birth, the other quite late in life – are two sides of the same coin,” said William C. Mobley, MD, PhD, professor and chair of the Department of Neurosciences at UC San Diego School of Medicine. “Autopsies of DS and AD brains reveal virtually identical pathologies – the same telltale amyloid plaques and neurofibrillary tangles.”
Under the auspices of the Alzheimer’s Disease Cooperative Study (ADCS), based at the University of California, San Diego School of Medicine, a new clinical study called the Down Syndrome Biomarker Initiative (DSBI) was launched in March 2013. According to the study’s director, Michael Rafii, MD, PhD – medical director of the ADCS – its aim is to discover indicators of Alzheimer’s and study progression of the disease, with the ultimate goal of better understanding brain aging and AD in adults with Down syndrome.
The three-year pilot study has enrolled 12 participants, aged 30 to 60 years of age. Study participants will be screened for various biomarkers of AD, using tests that include three types of brain scans, retinal amyloid imaging and blood tests, among others.
“Findings to date using MRI and amyloid PET scans indicate that individuals with Down syndrome show the same brain patterns as those in the general population with the earliest stages of the memory-robbing disease, called prodromal AD,” said Rafii.  He added that indications of increased brain amyloid deposition – the insoluble protein aggregates found in the brains of patients with AD that are thought to be an underlying cause of the disease – is similar in individuals with DS and those in the general population with AD.
People with amyloid deposition in the brain experience progressive cognitive deterioration. Brain atrophy – shrinking of the brain’s hippocampus – caused by the amyloid buildup, affects routine functional abilities, ultimately leading to complete physical disability.
“By understanding the progression of the disease in people with Down syndrome and those in the general population, we hope discoveries can be made in each group that can be shared between both populations,” said Rafii. 
The design of the DSBI pilot study is patterned after the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which began in 2004 to establish neuroimaging and biomarker measures of AD.  ADNI tracked the changes taking place in the brains of 800 older people, either free of symptoms or diagnosed with late-stage mild cognitive disorder and early Alzheimer’s disease. 
“Our aim is for the Down Syndrome Biomarker Initiative to mirror ADNI’s successes,” Rafii said.  “ADNI has helped the international Alzheimer’s research community learn significant lessons about the pathology and biomarkers of AD, which in turn has driven new ways of looking at the disease and new studies that we hope will lead to viable treatments. We are confident we can do the same thing for Down syndrome.” 
The 12-subject pilot study at UC San Diego is funded by Janssen Research & Development, LLC.  The research is projected to expand into a five-year, 1,000-subject international study.

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Media Contact: Debra Kain, 619-543-6163, ddkain@ucsd.edu; Jeffree Itrich, ADCS, 858-246-1317, jitrich@ucsd.edu