Study of Highly Prevalent Alzheimer’s Disease in Down’s Syndrome Adults may Yield AD Biomarkers

Dr. Michael Rafii

UC San Diego

Grant Program:

Clinical Neuroscience Research

Funded in:

April 2014, for 3 years

Funding Amount:


Lay Summary

Study of highly prevalent Alzheimer's disease in Down's syndrome adults may yield AD biomarkers

This longitudinal study of adults with Down’s syndrome, who have a high probability of developing mild cognitive impairment that eventually progresses to dementia superimposed on the existing intellectual disability, may identify biomarkers that occur at the earliest stages of Alzheimer’s disease.

Nearly every adult with Down’s syndrome will develop the plaques and tangles in the brain that are the hallmarks of Alzheimer’s disease (AD), and nearly 80 percent will develop clinical dementia. This astonishingly high rate of AD in Down’s syndrome is thought to occur because people with Down’s syndrome have three instead of two copies of chromosome 21, and it is on chromosome 21 where the gene resides that produces the “Alzheimer’s Precursor Protein (APP).” This protein generates excess amounts of amyloid, which forms plaques in between brain cells and disrupts communication. By their 40’s, adults with Down’s syndrome begin to develop mild cognitive impairment (MCI) and four out of five of these adults subsequently develop AD. By studying a large number of adults with Down’s syndrome over time, therefore, scientists anticipate that they will be able to identify key factors that occur during the trajectory from MCI to dementia in this population. What they find is likely to apply to development of AD in the general population.

Dana is being asked to provide partial support of a collaborative funding arrangement with other public and private sector entities including the National Institutes of Health, the Alzheimer’s Association and pharmaceutical industry. A total of 200 adults with Down’s syndrome, who are between the ages of 20 and 60, will participate in the three-year study. The investigators will perform a series of tests annually in each participant to investigate relationships among demographic and genetic factors, cognitive and clinical assessments, and imaging and biochemical markers.

They will measure amyloid in the brain and CSF (cerebrospinal fluid, which bathes the brain and spinal cord), will measure a host of biochemical factors in blood samples, and will measure cognitive and clinical changes. They anticipate that the testing will enable them to identify biomarkers that indicate or predict AD-related changes at the earliest feasible stage. Ultimately this study may provide the framework for multi-center trials of treatments that target the biomarkers for AD in Down’s syndrome.

Significance: If biomarkers of cognitive impairment and Alzheimer’s disease onset and progression in Down’s syndrome are found, the biomarkers can be used to assess the effects of experimental therapies designed to prevent or slow the dementing process.

Investigator Biographies

Dr. Michael Rafii

Dr. Rafii is Director of the Memory Disorders Clinic and Assistant Professor of Neurosciences at UC San Diego. He is also Medical Director of the NIH-funded Alzheimer’s Disease Cooperative Study and Attending Neurologist at the Shiley-Marcos Alzheimer’s Disease Research Center. He specializes in dementias such as Alzheimer’s disease.

Dr. Rafii also directs the Adult Down Syndrome Clinic. He is Clinical Director of the UCSD Down Syndrome Research and Treatment Center and serves as Principal Investigator on numerous clinical studies. Dr. Rafii also serves on the National Task Group on Intellectual Disabilities and Dementia Practices of the American Academy of Developmental Disorders. As Director of the Neurology Residency Training Program, Dr. Rafii is involved in the training of the next generation of neurologists.
He received his MD and PhD from Brown University School of Medicine and conducted neurogenetics research at Harvard Medical School. Dr. Rafii went on to complete his Neurology residency at the Johns Hopkins Hospital, where he was chief resident. He then completed a fellowship in Dementia at UC San Diego.