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2022 Alzheimer's Association Research Grant (AARG)

Revealing Combinations of Haplotypes Associated with Alzheimer Disease

Can patterns of genetic change in the brain work together to increase a person’s risk of Alzheimer’s?

Sharlee Climer, Ph.D.
University of Missouri
St. Louis, MO - United States


Genes play an important role in Alzheimer’s. For most individuals who have late-onset Alzheimer’s, the genetic mechanisms are complicated. The most prominent genetic variation thought to increase risk in some populations for late-onset Alzheimer’s is APOE-e4, in a gene that provides instructions for making ApoE protein. However, there are also many other genetic variations that likely impact Alzheimer’s risk, many of which have not been identified. Recent studies indicate that some genes may increase risk of Alzheimer’s through interactions with other genes.

One factor that has hindered the search for Alzheimer’s genes relates to the standard risk gene-identifying technique called genome-wide association studies (GWAS). Traditional GWAS techniques only examine one gene variation at a time, and the studies are often not designed to identify disease-related genetic interactions. In response to these limitations, Dr. Sharlee Climer and colleagues have developed a novel technique called BlocBuster to identify patterns of change in a large group of gene variations (haplotypes) instead of single gene variations like traditional GWAS methods. Their initial studies suggest that these patterns can reveal mechanisms underlying Alzheimer’s more effectively than can individual gene variations.  

Research Plan

Dr. Climer and colleagues will build upon their initial work by examining a larger study of gene variations from individuals with Alzheimer’s; they will collaborate with several large studies of aging. With this data, they will use the BlocBuster technique to find potential Alzheimer’s haplotypes (patterns of changes in multiple genes). They will then use a new computer software program to identify how combinations of these haplotypes may interact to increase risk of Alzheimer’s and identify potential biological mechanisms.


Results from Dr. Climer’s project could shed new light on the role of genetics in Alzheimer’s and related dementias. They could also lead to novel methods of identifying disease risk genes and other biological mechanisms behind Alzheimer’s. 

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