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2015 Grants - Liu
Dyrk1A in Early Onset of Alzheimer’s Pathology in Down Syndrome
Fei Liu, Ph.D.
Research Foundation for Mental Hygiene, Inc. at NYS Institute for Basic Research
Menands, New York
2015 Understanding the Development and Devising Treatments for Alzheimer’s Disease in Individuals with Down Syndrome Grant
Do high levels of the protein Dyrk1A in people with Down syndrome contribute to the development of Alzheimer’s disease?
Down syndrome is a condition in which people are born with an extra copy of chromosome 21. Chromosomes contain all of our genes, and scientists believe that the extra copies of genes on chromosome 21 lead to health issues associated with Down syndrome. People with Down syndrome have a high risk of developing Alzheimer’s disease, and the disease often begins to develop when the individuals are in their 30s and 40s.
One of the chromosome 21 genes that may link Down syndrome and Alzheimer’s is the gene that codes for a protein called dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A). Dyrk1A normally helps to regulate cellular processes by adding chemical “tags” to other proteins to control their activity. When Dyrk1A levels are high, as is the case in people with Down syndrome, protein processing and activity may become abnormally altered.
Alzheimer’s disease is marked by the accumulation of amyloid plaques and tau tangles in the brain. Fei Liu, Ph.D., and colleagues recently discovered that high Dyrk1A levels alter the processing of amyloid and tau proteins, leading the researchers to predict that Dyrk1A overproduction in Down syndrome may promote the brain changes associated with Alzheimer’s disease.
For their current work, Dr. Liu’s team will examine how Dyrk1A affects the production and processing of beta-amyloid and tau proteins in brain tissue from people with Down syndrome who had Alzheimer’s. They will also use mice genetically engineered to have a Down syndrome-like condition to determine if inhibiting Dyrk1A can prevent the abnormal build-up of beta-amyloid and tau in the brain. Finally, using cells grown in laboratory dishes, they aim to discover the specific molecular mechanisms by which Dyrk1A modifications lead to the formation of amyloid plaques and tau tangles.
This work may provide new insight into how high levels of Dyrk1A contribute to Alzheimer’s disease in people with Down syndrome and help to improve our understanding of sporadic Alzheimer’s as well. A better understanding of these molecular mechanisms could lead to the identification of novel targets for the development of drug treatments to prevent or slow the disease process.
Co-funded by the Alzheimer’s Association, Global Down Syndrome Foundation and Linda Crnic Institute for Down Syndrome