Researchers Study Alzheimer’s Disease in People with Down Syndrome

Studies May Lead to Earlier Diagnosis and Treatment of Alzheimer’s Disease in All Patients

The risk of Alzheimer’s disease—the most common cause of dementia—increases as a person ages. But the risk of Alzheimer’s is increased dramatically for adults with Down syndrome.

At age 40, individuals with Down syndrome already have the neuropathological changes of Alzheimer’s disease, including the telltale buildup of amyloid plaques and tau tangles that precede symptoms. The early buildup occurs because people with Down syndrome carry an extra copy of chromosome 21, which contains a gene that produces a protein that is a precursor for amyloid.

Ninety percent of individuals with Down syndrome will have developed Alzheimer’s disease by age 70 (in the general population, 11 percent of people over age 65 and 32 percent of people over age 85 have Alzheimer’s). However, there is wide variation in age at onset of dementia, ranging from under 40 to over 70 years of age, suggesting that additional genetic, biological, and environmental factors may be important modifiers of risk that accelerate or slow disease progression.

New studies at Columbia are designed to explain why some people with Down syndrome develop Alzheimer’s disease earlier than others and why some people with Down syndrome may never develop the disease. With funding from the NIH, Nicole Schupf, PhD, DrPH, will identify biomarkers for Alzheimer’s disease in people with Down syndrome, which may help researchers predict who will develop Alzheimer’s in all groups of people. Dr. Schupf is professor of epidemiology at CUMC in Columbia’s Taub Institute for Research on Alzheimer’s Disease and the Aging Brain and the Departments of Neurology and Psychiatry.

The NIH's Laurie Ryan, PhD, discusses the new research:

Investigating Alzheimer's in People with Down Syndrome

Many researchers believe that future Alzheimer’s disease treatments may be most effective in the early stages of the disease, before the onset of symptoms and before irreversible neuron loss has occurred. Dr. Schupf’s work will identify biomarkers that can predict the risk of developing Alzheimer’s disease in people with Down syndrome with no symptoms of the degenerative disease.

The study focuses on a longitudinal and multidisciplinary determination of key biomarkers that are likely to define the progression from normal aging to onset of dementia, including levels and rates of change in blood-based biomarkers such as b-amyloid peptides, protein, inflammatory and lipid profiles, measures of amyloid and tau concentration in cerebrospinal fluid, neuroimaging-based changes, PET studies of brain amyloid uptake, and genetic polymorphisms. These biomarkers will be combined to develop the most valid indicators of preclinical and early stages of Alzheimer’s. The goal is to develop a noninvasive test to detect Alzheimer’s disease in individuals with Down syndrome and in the broader population.

The grant for this prospective study is part of an NIH initiative, Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome, that supports two collaborative teams seeking Alzheimer’s Disease biomarkers in people with Down syndrome. Dr. Schupf leads a team of investigators from Columbia University Medical Center, the University of California, Irvine, Kennedy Krieger Institute/Johns Hopkins University, Massachusetts General Hospital/Harvard, the New York State Institute for Basic Research in Developmental Disabilities, and the University of North Texas Health Sciences Center. The second team is headed by Benjamin Handen, PhD, from the University of Pittsburgh. The two projects will share $37 million in funding over the next five years.