Relationship Between Alzheimer’s and Down Syndrome Explored

Since the most common chromosome abnormality results in down syndrome, it is very prevalent, with 1 in 700 newborns in the U.S. being diagnosed every year. It occurs because of an extra copy of chromosome 21, specifically. 25% of those with down syndrome will have symptoms of Alzheimer’s dementia by 35 and 75% of them will show symptoms at the age of 65.

People with down syndrome are now living much longer than they were just a few decades ago, with the average life expectancy being 25 years in 1983, compared today’s average life expectancy for them, which is 60 years. This means that the cases of people that have down syndrome and Alzheimer’s will undoubtedly increase over time. Conducted at the Sanford-Burnham Medical Research Institute, a study found that mice with characteristics of down syndrome and Alzheimer’s had less of a protein known as sorting nexin 27 (SNX27) than normal mice. This protein maintains receptors on brain cells. If it is compromised, it can lead to cognitive deficits.

In addition to facilitating the proper functioning of neurons, the SNX27 protein also influences the production of beta-amyloid proteins. These proteins accumulate with plaques in the brain and are the main cause of Alzheimer’s disease. When interacting with the gamma-secretase enzyme, which produces beta-amyloid, the SNX27 protein completely disables the enzyme, leading to a decrease in beta-amyloid production.

Therefore, if people have decreased amounts of SNX27, there will be more gamma-secretase in the body, leading to an increase in beta-amyloid proteins, which can cause Alzheimer’s. Interestingly enough, the team found that lower amounts of SNX27 in mice and people with down syndrome are the result of an extra copy of an RNA molecule known as miRNA-155. This molecule is actually encoded by chromosome 21—the same chromosome affecting down syndrome, and influences the production of SNX27.

To recap the information presented, the extra copy of chromosome 21 present in down syndrome increases the levels of miRNA-155, and that decreases the amount of SNX27 in the body. These decreased amounts of SNX27 leads to a higher number of gamma-secretase, and this leads to an increase in beta-amyloid proteins, which causes Alzheimer’s disease. Researchers discovered that producing new copies of the gene encoding SNX27 fixed the memory deficit in mice with down syndrome. They are looking to develop a test to pinpoint molecules that will decrease miRNA-155 levels, and molecules that will facilitate interactions between gamma-secretase and SNX27.

Author

Gary Starkman Dr. Starkman, a top Neurologist in NYC, is the Medical Director and founder of New York Neurology Associates. He is Board Certified in Neurology with a subspecialty certification in Pain Medicine.