Description: BYU Professor John Kauwe of the Biology Department is an award-winning, internationally-acclaimed researcher specializing in Alzheimer’s disease genetics. He is working with George Washington University and Utah State University in this expansive study to better understand the genetic architecture that makes up AD.
Start: September 1, 2012
End: December 31, 2017
- Sponsor: NIH
- Principal Investigator: Dr. John Kauwe
- Co-PI: Dr. Perry Ridge
- Website: http://kauwelab.byu.edu
Alzheimer’s disease (AD) causes an irreversible deterioration of the brain, slowly erasing memories, disrupting thought processes, and causing disorientation. While this condition is not immediately fatal, it results in an eventual decline that usually becomes severe enough to interfere with simple physical tasks, behavioral responses, and bodily functions. It is estimated that around 5 million Americans currently have Alzheimer’s, and it is ranked as the sixth leading cause of overall death in the United States, moving up to the third cause of death for elderly individuals.
Until recent years, the biggest known risk factor for Alzheimer’s was age, with approximately 80% of individuals with AD age 75 or older. Dr. John Kauwe is working with George Washington University and Utah State University to compile data from more than 3,000 samples. This has allowed them to understand more accurately where Alzheimer’s comes from, and how genes interact and modify to set the rate of disease progression.
Genes are segments and sequences of DNA that detail out certain functions or characteristics for the body. They are formed with chains of organic molecules called nucleotide bases (A, C, G, and T). A single gene can be made up of numerous combinations of nucleotide bases, and each base variation (scientifically known as single nucleotide polymorphism or SNP) can lead to a different medical condition or physical characteristic. AD is more complex than testing if individuals have a specific gene; its severity depends on the interactions and placements of these genetic variations. Dr. Kauwe’s research involves performing a “genome-wide screen”—an examination of many people’s DNA to find SNP variations. Dr. Kauwe’s team uses SNPs as biological markers, noting when they occur in or near certain genes. This process allows them to see the interplay that affects normal genes and contributes to the disease.
The researchers are also working to understand how certain genes are “pleiotropic”, or have multiple effects on the body. A key example of this in relation to AD is protein aggregation, or proteins that, instead of folding properly, clump together unnaturally. Protein aggregation causes twisted tissue in the brain—neurofibrillary tangles—which are the primary markers of AD. A key reason for this distortion may be a pleiotropic gene that modifies the “tau level”. Tau proteins are proteins that give strength to the cell structure, and are largely found in the central nervous system, which is made up of the brain and the spinal cord. Understanding the weakening of the central nervous system will help doctors determine how quickly or slowly a patient’s Alzheimer’s will progress.
In total, this project is the largest study of its kind, drawing on more than 3,000 samples with cerebrospinal fluid biomarker measurements and clinical evaluations—2,000 of which also have whole-genome marker data. At least 1900 of these cases have longitudinal measurements of the disease progression, meaning that each provide information from follow-up appointments. They will analysis this data against 20,000 other cases (people confirmed to have AD) and 30,000 controls (healthy, similar individuals without AD). This will allow the researchers to make comprehensive comparisons that will shows genetic patterns that make up this disease.
While this study is significant because of its size, its most noted legacy will be in furthering the fight against AD. Dr. Kauwe’s efforts, and those of his team, will provide a more complete genetic picture of AD. Improved understanding of this specific disease will allow doctors to find better treatment and prevention strategies. In-depth research of genetics and how they influence AD may also connect to answers about other degenerative diseases.