2023 Alzheimer's Association Research Grant (AARG)
Mechanisms of Complement Mediated Synaptic Removal Following Tauopathy
How does tau contribute to impaired synaptic function in Alzheimer’s?
Matthew Benskey, Ph.D.
Michigan State University
Grand Rapids, MI - United States
Background
One of the hallmark brain changes associated with Alzheimer’s is the accumulation of tau tangles. Normally, tau is a protein that functions to transport nutrients and help nerve cells maintain their proper structure. Nerve cells in the brain connect and communicate to each other through specialized structures called synapses which are important for overall brain health. In Alzheimer’s and other dementias, tau tangles can prevent the removal of damaged synapses, leading to impaired nerve cell communication and increased nerve cell death. However, the exact mechanisms by which tau impairs synaptic function in Alzheimer’s is unknown.
Dr. Matthew Benskey and colleagues have discovered that a specific protein that physically interacts with impaired synapses, called complement C1q, is elevated in the brains of individuals who had Alzheimer’s.
Research Plan
Dr. Benskey and team will investigate the association between complement C1q and tau in the nerve cells of genetically engineered Alzheimer’s-like mice. They will also measure synapse damage associate the levels of synapse damage with complement C1q and tau levels in nerve cells from the same mice. Next, the team will identify other proteins that are located within damaged synapses in brain tissue from individuals who had Alzheimer’s to identify potential mechanisms linking tau and complement C1q in Alzheimer’s.
Impact
The results of these studies will determine if tau affects nerve cell communication by preventing the removal of damaged synapses, and possibly lead to new interventions for the prevention of tau-mediated Alzheimer’s progression.