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2023 Alzheimer's Association Research Fellowship (AARF)

Can Subtyping of Alzheimer’s Heterogeneity Improve Clinical Trial Design?

How may identifying individuals with specific types of Alzheimer’s improve our ability to test and develop disease treatments?

Lyduine Collij, Ph.D.
Amsterdam University Medical Center, VUmc
Amsterdam, Netherlands


Although Alzheimer’s is commonly thought to be a single disease, evidence has revealed several different forms of the disorder. Alzheimer's progression differs from individual to individual, and its course may be determined by the state of one’s brain blood vessel health, genetic make-up or levels of disease related proteins (including beta-amyloid, a hallmark brain change in Alzheimer’s) in the brain, blood and cerebrospinal fluid (or CSF, the biological fluid surrounding the brain and spinal cord). This “heterogeneity” of Alzheimer’s has made the search for disease-modifying drugs challenging. Certain treatments may have the greatest impact on individuals with specific dementia-related biological changes, yet clinical trials have not often looked for these optimal population “subtypes” when recruiting to test candidate drugs. 

Research Plan

Dr. Lyduine Collij and colleagues will work to identify a variety of disease subtypes that can be used in selecting individuals for Alzheimer’s clinical trials. They will collect brain scan results, cognitive test data, and blood and CSF analyses from about 3,000 individuals and use a sophisticated analytical technique to identify disease subtypes based on groups of disease-related factors. First, the researchers will identify subtypes of individuals based on how abnormal beta-amyloid levels and brain blood vessel disorders work to impact brain health. They will further define these subtypes by examining their interactions with other disease factors, such as altered immune cell activity and disease-related proteins in the blood and CSF. Finally, Dr. Collij and colleagues will test the reliability of these subtypes in theoretical clinical trials designed to assess cognitive decline and the clumping of disease-related brain proteins.  


Dr. Collij’s project could clarify how disease subtyping can improve the ability of clinical trials to assess disease treatments. Such work may lead to better methods of modifying disease progression at an early stage, before clinical symptoms become evident.

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