Down Syndrome and Its Clues About Alzheimer's Disease

We believe that a focus on Down syndrome will provide important clues about Alzheimer’s disease. 

At least 20 years before any symptoms of Alzheimer’s disease begin to appear, pathological changes in the brain that characterize the disease have already started. Therefore, a focus on the early, pre-clinical phase of Alzheimer’s disease may be optimal when developing new approaches to diagnosis, treatment, and intervention. However, 90 percent of Alzheimer’s disease is sporadic, meaning that it occurs at random in people without a family history of the disease, making it difficult to identify people in the general population with early Alzheimer’s disease pathology who are not yet showing symptoms of the disease. Here at the University of Colorado (CU) Alzheimer's and Cognition Center, much of our research has a special focus on people with Down syndrome, who we believe can help us overcome this research barrier.

Only two human populations have a high risk of developing Alzheimer’s disease at a young age. One population consists of people with a family history of Alzheimer’s disease who carry a causal mutation in one of three genes, including the amyloid precursor protein (APP) gene, and the second consists of people with Down syndrome. People with Down syndrome (trisomy 21) carry three, instead of two, copies of chromosome 21, which includes the APP gene. Mostly due to the fact that they have three copies of the APP gene, people with Down syndrome have Alzheimer’s disease brain pathology by age 40, and most develop dementia by age 60. Because people carrying familial Alzheimer’s disease-causing mutations are extremely rare, we believe that people with Down syndrome may offer the best opportunity for studying the development of Alzheimer’s disease across the lifespan, because they are known to develop Alzheimer’s disease brain pathology and can be studied from an early age.

Although most people with Down syndrome eventually develop dementia, around 30% do not. This suggests that a subset of people with Down syndrome are somehow protected from dementia, even though they have Alzheimer’s disease brain pathology. A similar observation has been made in the typical aging population, where people without dementia have been identified with high levels of Alzheimer’s disease brain pathology at autopsy, but at a lower frequency of around 20%. However, it would again be very difficult and expensive to identify this group of people in the general population. Therefore, people with Down syndrome also provide an ideal opportunity to study the early stages of Alzheimer’s disease and to uncover protective mechanisms that may prevent dementia. 

Support for our focus on people with Down syndrome comes from Dr. Potter’s discovery that every person with typical age-related Alzheimer’s disease develops many DS-like (trisomy 21) cells and other types of aneuploid cells (cells with abnormal numbers of chromosomes) throughout their bodies, including neurons in the brain. His lab has recently discovered that other neurodegenerative brain diseases also appear to be linked to trisomy 21 and other chromosomal aneuploidies, suggesting that aneuploidy-focused prevention and treatment strategies may apply to many brain diseases. Notably, Colorado is home to 4,000 people with Down syndrome, and the CU Alzheimer's and Cognition Center has strong partnerships with the Linda Crnic Institute for Down Syndrome at the University of Colorado, the Sie Center for Down Syndrome at Children’s Hospital Colorado, and the Global Down Syndrome Foundation in Denver.