2012 Grants - Gitcho

Age-Dependent Increases of Phosphorylated TDP-43 in APP Mice

Michael Gitcho, Ph.D.
University of Wisconsin-Madison
Madison, Wisconsin

2012 New Investigator Research Grant

TDP-43 is a protein found inside of cells that performs a number of functions that are critical to the cell. However, abnormal TDP-43 has been implicated in several neurological diseases such as amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) and some forms of dementia.

Michael Gitcho, PhD., and colleagues have been studying TDP-43 in mice that have been genetically engineered to have some of the same genetic mutations (an alteration in a person's DNA) found in people who have inherited forms of Alzheimer's disease. These mice develop many of the characteristic features of Alzheimer's disease as they age, including amyloid plaques in the brain. Dr. Gitcho and colleagues have observed that the TDP-43 protein in these animals is abnormally modified even before the animals develop amyloid plaques in the brain, possibly suggesting alteration of TDP-43 is an early event in the disease process.

Dr. Gitcho and colleagues have proposed more extensive studies of how TDP-43 becomes abnormally modified in these animals by the addition of phosphate chemical groups (phosphorylation). They will also study how this modification leads to the clumping of TDP-43 into abnormal deposits, and how TDP-43 interacts with amyloid plaques. These studies may reveal new insights into the biochemical pathways that produce amyloid plaques in Alzheimer's disease.