2023 Alzheimer's Association Research Grant (AARG)
Central auditory deficits in the pathogenesis of Alzheimer's disease
Does hearing loss hold early clues to Alzheimer’s?
Jun Hee Kim, Ph.D.
University of Michigan
Ann Arbor , MI - United States
Background
Hearing loss is common in individuals as they age, and it is associated with the memory and thinking difficulties related to Alzheimer’s. With aging, individuals lose specialized cells in the ear drum that can detect high-pitched sounds. In contrast, as the characteristic plaques and tangles of Alzheimer’s develop inside the brain, this may disrupt how the brain processes sound signals, and result in a pattern of hearing loss that is distinct from the typical age-related hearing loss.
Dr. June Hee Kim plans to study the auditory (hearing) system in genetically engineered Alzheimer’s-like mouse model. They will do this by examining the hearing of these mice early in life, before any memory difficulties develop. Dr. Kim believes that changes to a material called myelin, and the cells that produce it (called oligodendrocytes) disrupt how well the auditory system in the brain can carry sound signals, in ways that reduce hearing capabilities. Myelin surrounds the thin axonal connections that carry electrical signals between one brain cell and another, and is thus essential for accurate transfer of information about sounds in the brain.
Research Plan
Dr. Kim and colleagues will test auditory system function in genetically-engineered Alzheimer's-like mice using a non-invasive technique called auditory brainstem response. This method allows researchers to monitor how sound signals are relayed from the ear to the different parts of the brain that process sounds in a chain-like fashion. Initial experiments have found impairments in sound processing in the brains of these mice, even before memory problems arise. Further experiments will study these changes at 2, 3, 6, and 9 months of age.
The project will also look for the cellular reasons for these changes. One belief is that the Alzheimer’s-related plaque protein damages oligodendrocyte cells, which in turn would alter myelin production. Dr. Kim will examine brain tissue under a microscope to see how the oligodendrocyte numbers and myelin amounts compare to mice that do not carry the Alzheimer’s-related mutations.
Impact
This research may help identify the pathways behind sound processing and how this is impacted in early stages of Alzheimer’s. This also has the potential to provide key information for developing new treatment strategies for slowing hearing loss, and potentially memory impairments, in Alzheimer’s.