Three kinases, or proteins, may play a role in memory loss linked with Alzheimer's disease, a new study shows.
The three kinases were found to cause a malfunction in tau, a protein critical to the formation of the microtubule bridges within brain cells, or neurons. These bridges support the synaptic connections that, like computer circuits, allow neurons to communicate with each other.
The study was conducted by a scientific group led by the Translational Genomics Research Institute (TGen), a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results.
TGen investigators created sophisticated tests to look at all 572 known and theoretical kinases within human cells. They identified 26 associated with the phosphorylation of tau. Of these 26, three of them - EIF2AK2, DYRK1A and AKAP13 - were found to cause hyperphosphorylation of tau, permanently dismantling the microtubule bridges.
These findings are published in this month's edition of BMC Genomics.
"The ultimate result of tau dysfunction is that neurons lose their connections to other neurons, and when neurons are no longer communicating, that has profound effects on cognition - the ability to think and reason," said Dr. Travis Dunckley, an Associate Investigator in TGen's Neurodegenerative Research Unit and the scientific paper's senior author.
Tau performs a critical role in the brain by helping bind together microtubules, which are sub-cellular structures that create scaffolding in the neurons, allowing them to stretch out along bridges called axons. The axons support the synaptic, or chemical, connections with other neurons.
Under normal circumstances, kinases regulate tau by adding phosphates. This process, called tau phosphorylation, enables the microtubules to unbind and then bind again, allowing brain cells to connect and reconnect with other brain cells.
"That facilitates synaptic plasticity. It facilitates the ability of people to form new memories - to form new connections between different neurons - and maintain those memories. So, it's an essential function," Dr. Dunckley said.
However, sometimes the tau protein becomes hyperphosphorylated, a condition in which the tau creates neurofibrillary tangles, one of the signature indicators of Alzheimer's.
"When tau protein is hyperphosphorylated, the microtubule comes apart - basically destroying that bridge - and the neurons can no longer communicate with each other," Dr. Dunckley said.
"This paper shows, for the first time, these three kinases affect Alzheimer's disease-relevant tau hyperphosphorylation, in which most of the tau protein is now driven into a permanently phosphorylated form," Dr. Dunckley said.