2023 Alzheimer’s Association Leveraging Model & Data Resources to Advance Alzheimer’s and Dementia Discovery Program (ALZDISCOVERY)
Super-Resolution Ultrasound to Measure Vascular Pathology in a LOAD Model
Can a novel brain scanning technique assess dementia-related changes in the tiniest blood vessels?
Daniel Llano, M.D., Ph.D.
University of Illinois, Urbana-Champaign
Urbana, IL - United States
Background
As individuals age, blood vessels can become damaged, hindering blood flow in the brain and other parts of the body. Studies show that vascular (blood vessel) damage may impact an individual’s risk for many brain diseases, including late-onset Alzheimer’s disease (LOAD), the most common form of Alzheimer’s. Vascular damage often occurs in tiny blood vessels (or microvessels) located deep within the brain – blood vessels that traditional imaging techniques have been unable to reveal with sufficient resolution and clarity. This lack of clarity has hampered the ability of scientists to identify how microvascular damage develops and how it promotes cognitive decline and other Alzheimer’s-related brain changes.
To address these problems, Dr. Daniel Llano and colleagues have been developing an improved imaging technique based on ultrasound (the use of high-frequency sound waves to view structures inside the body). Their technique, called ultrasound localization microscopy (ULM), can visualize microscopic damage to tiny blood vessels, as well as miniscule changes in microvessel blood flow.
Research Plan
Dr. Llano and colleagues will now test their ULM method in mice genetically engineered to develop the APOE-e4 or APOE-e3 gene variations. APOE-e4 has been linked, in certain populations, to increase risk of Alzheimer’s and lead to dementia-related blood flow problems and subsequent cognitive decline, while APOE-e3 has been shown to not impact such changes. First, the researchers will use ULM to compare how the structure and function of microvessels differ in mice with APOE-e4 from mice with APOE-e3. They will also compare how microvascular problems impact cognition in the animals. Next, the mice will undergo a 3-month endurance exercise program, after which Dr. Llano’s team will analyze changes in behavior and use ULM to examine microvascular changes. Specifically, the team will assess how exercise may have protected the mice from APOE-related behavioral decline, and how such protection may have promoted microvascular health.
Impact
Dr. Llano’s project could identify a novel tool for studying microvascular health in people at risk of Alzheimer’s. It could also lead to novel methods of diagnosing and treating dementia.