Alzheimer’s, sleep disruption and fruit flies

Professor Doris Kretzschmar and graduate student Eve Lowenstein examining an image of a fruit fly brain.

We congratulate Institute Associate Professor Doris Kretzschmar, Ph.D., upon her recently awarded National Institute of Aging R01 grant titled Connecting nuclear functions of Tau with pathology in Alzheimer’s disease and other Tauopathies. Tau protein is found in brain cells, and has been associated with human brain diseases. The project focuses on investigating how mutations in Tau that are associated with human diseases (such as frontotemporal dementia) affect the function of Tau.

Alzheimer’s disease and other age-related neurodegenerative diseases are becoming an increasing burden for patients, caregivers, and the health care system. Though Alzheimer’s disease is mostly known for its effects on memory, patients also show a disrupted sleep pattern with often becoming agitated and anxious late during the day (known as sundowning) and restlessness during the night. It is well documented that memory is affected by poor sleep and these sleep disruptions are not just a side effect but are likely to further enhance the memory loss and cognitive decline in these patients. However, why sleep disturbances occur with Alzheimer’s disease and dementia is not understood.

A hallmark features of Alzheimer’s Disease and other dementias is the accumulation of the Tau protein into a protein involved in the integrity of the cells cytoskeleton. An intact and functioning cytoskeleton allows a nerve cell to maintain its structure, transport proteins within the cell and to interact with other nerve cells. To determine how changes in Tau may lead to sleep disruptions the Kretzschmar Lab used the well-established Drosophila (better known as fruit flies) model. In their recent publication, the lab showed that Drosophila expressing a mutated human Tau protein do show sleep disruptions while flies with a normal human Tau do not. Further analyzing these flies, they found that the mutant Tau caused changes in the cytoskeleton of nerve cells that regulate sleep. These cells show daily fluctuations in their connectivity, whereby they form more contact zones to other nerve cells during the day and less during the night. However, when these cells contain the mutant Tau protein they are not able to reduce their contact zones during the night, thereby disrupting the day/night changes in these cells required to regulate sleep.

Learn more about Dr. Doris Kretzchmar and the Kretzchmar Lab.

Learn more by viewing the publication: Disease-Associated Mutant Tau Prevents Circadian Changes in the Cytoskeleton of Central Pacemaker Neurons.