2024 Alzheimer's Association Research Grant (AARG)
Defining the Role of Clonal Hematopoiesis in Alzheimer’s Disease
Could genetic variations associated with a blood condition help protect against Alzheimer’s?
Frederik Damm, M.D.
Charité - Universitätsmedizin Berlin
Berlin, Germany
Background
Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by unusual genetic variations inside blood cells. Emerging research suggests that CHIP may reduce Alzheimer’s risk. While several previous studies have identified genetic variations in CHIP, the link between CHIP and Alzheimer’s is poorly understood. It remains unclear whether CHIP may also reduce the risk of conditions that often precede Alzheimer’s, such as subjective cognitive decline (SCD) or mild cognitive impairment (MCI).
Research Plan
In the current study, Dr. Frederik Damm and team will investigate associations between CHIP and damage to the brain, using cognitive testing data and biological samples donated by healthy individuals and those with SCD, MCI, or Alzheimer’s. They will leverage an existing study at their institution called the German Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort that has up to 8 years of annual test results and biological samples provided by participants.
The researchers will first analyze genetic material (DNA samples) provided by the participants for CHIP-related genetic variations. They will identify any associations between CHIP and cognitive ability. By studying groups of participants with SCD, MCI, and Alzheimer’s separately, the researchers will be able to clarify specific links between CHIP variations and cognitive symptoms. Next, the researchers will measure levels of immune cell molecules using samples of blood and cerebrospinal fluid (CSF), which is the fluid that surrounds the spinal cord. This will help Dr. Damm and colleagues understand how CHIP might alter the body’s normal immune response to Alzheimer’s. Finally, the research team will use advanced statistical methods to investigate genetic changes over time in study participants with CHIP. They will determine if the quality or quantity of CHIP-related genetic variations are stable or dynamic over time, and how this differs depending on a participants’ cognitive status.
Impact
The possibility that CHIP-related genetic variations might help protect against Alzheimer’s is an important area of study. By dissecting the exact role of CHIP in Alzheimer’s, this study provides foundational data that could be used by others to further investigate biological mechanisms and therapeutic opportunities linking the two conditions.