Genomics research has significantly advanced the scientific understanding of Alzheimer's disease, the discovery of promising investigational treatments and the accelerated evaluation of treatments to prevent the disease. Eventually, it could help doctors determine which people are most likely to benefit from a particular treatment.
Genomics research refers to the study of genes, the mechanisms by which they are turned on or off and the extent to which they contribute to normal and abnormal functions.
Genetic Risk Factors for Alzheimer's disease
Inherited genes are thought to account for about 70 percent of the risk for developing Alzheimer's disease.
A gene called APOE4 is a major genetic risk factor for Alzheimer's. About 20-24 percent of the population carries one copy of the APOE4 gene (inherited from one parent), about 2-3 percent of the population has two copies of the gene (inherited from both parents), and each additional copy of the gene increases a person's chance of developing the disease.
There are many other genes that contribute to a person's risk in a much more modest way but that could still shed light on the biological processes underlying the disease and could help in the discovery of new treatments. To date, researchers have identified about 10 of these "Alzheimer's susceptibility genes." Due to advances in our ability to read each person's "genetic book" and a new spirit of collaboration in the field, researchers are likely to identify many more susceptibility genes.
In addition, about 200 misspellings of three inherited genes, known as PS1, PS2 and APP, are known to cause people to develop Alzheimer's disease in a person's 30s, 40s, and 50s. Individuals who inherit one of these genetic mutations are virtually certain to develop early-onset Alzheimer's. Their children have a 50/50 chance of inheriting the same gene.
Banner Alzheimer's Institute (BAI) researchers are internationally known for their efforts to detect and track the earliest brain changes in cognitively normal people at different levels of genetic risk for Alzheimer's.
BAI researchers have been working in partnership with colleagues from Mayo Clinic Arizona to study cognitively normal people at three levels of genetic risk for Alzheimer's. They have been working with colleagues at the University of Antioquia in Medellin, Colombia in the study of the world's largest extended family of early-onset Alzheimer's mutation carriers and non-carriers. Their findings have been published in leading scientific and medical journals. Among their contributions, they have:
- Detected some of the earliest brain changes associated with the predisposition to Alzheimer's disease, some of which are apparent almost five decades before the onset of memory and thinking problems. This research has helped to characterize the pre-clinical stages of Alzheimer's.
- Demonstrated how brain imaging techniques could be used to help clarify genetic and non-genetic risk factors for Alzheimer's.
- Proposed how imaging and other biological measurements could be used to rapidly evaluate therapies to prevent Alzheimer's. The Alzheimer's Prevention Initiative, an international collaborative led by BAI, is intended to usher in a new era in Alzheimer's prevention research, giving the field a chance to identify effective prevention therapies as quickly as possible.
- Made several pioneering contributions to the field in partnership with colleagues from the Translational Genomics Research Institute (TGen) by characterizing genes that are turned on and off in brain cells.
- Conducted the first genome-wide study of Alzheimer's, implicating new genetic risk factors for the disease and confirming others.
- Set a new precedent for the research community with the public release of these important datasets.
- Helped discover a gene that appears to influence normal memory performance and, on the basis of this discovery, a promising treatment to improve memory performance in people with and without Alzheimer's.
- Played a leading role in the creation of the Alzheimer's Disease Genetics Consortium, which continues to discover new genetic risk factors for Alzheimer's.