2022 Alzheimer's Association Research Grant (AARG)

Impact of Interneurons on Brain Networks in Alzheimer's Disease

How do specific nerve cells impact communication within the brain in Alzheimer’s?

Laura Jonkman, Ph.D.
VU University Medical Center Dept Anatomy and Neurosciences
Amsterdam, Netherlands

Background

Nerve cells in different brain regions communicate with each other via nerve cell networks or circuits that connect multiple brain regions. These networks have control over different types of cognitive functions, including memory. Studies suggest that brain changes in early Alzheimer’s may be associated with impaired communication between nerve cell networks. This impairment may be associated with loss of memory and other brain changes observed in Alzheimer’s. Understanding certain patterns in these brain networks may help predict Alzheimer’s-related brain changes, and open avenues for early and accurate detection and diagnosis. 

Research suggests that a specific type of nerve cell called interneurons are especially vulnerable to damage during Alzheimer’s disease. The loss of a small number of these cells can disrupt the activity of nerve cell networks needed for memory and learning. It is not yet understood why some nerve cells are more vulnerable to damage than others, but it may relate to how they are affected by the build-up of the proteins beta-amyloid or tau (two hallmark brain changes associated with Alzheimer’s).  Dr. Laura Jonkman and colleagues believe that mapping the distribution pattern of interneurons within brain regions may reveal their relationship to brain networks impacted in Alzheimer’s.

Research Plan

Dr. Jonkman and colleagues will study the distribution of specific types of interneurons in different brain regions impacted by Alzheimer’s and how these interneurons are associated with brain network functioning. In collaboration with the Netherlands Brain Bank (NBB) and the Normal Aging Brain Collection (NABCA), the research team will conduct brain scans (magnetic resonance imaging, MRI) on the brains of 40 individuals who had Alzheimer’s and 20 cognitively unimpaired individuals. Following the scans, the researchers will analyze samples of brain tissue from individuals who had Alzheimer's, selecting nine different brain regions to study the interneurons around the brain under a microscope.

Impact

If successful, the study results may help define the early changes in brain networks that occur in Alzheimer’s and open new paths for the development of drug therapies aimed to preserve nerve cell function in Alzheimer’s disease.