Australian researchers from Flinders University have offered new insight into how Alzheimer’s disease development relates to aspects of normal memory in people with healthy brains. They have discovered that the tau protein, which has shown to be an integral part of Alzheimer’s progression, also plays a critical role in learning in general.
“Our new study took a snapshot of all partners tau engages with to support normal brain function,” says senior study author Dr. Arne Ittner, a senior research fellow in neuroscience at the Flinders Health and Medical Research Institute, in a statement.
To conduct this work, the team used proximity labeling techniques to identify all proteins that tau interacts with inside of brain cells. This allowed researchers to create a better picture of the different proteins that interact with tau and understand the greater purpose that the interactions serve. Results show that while tau binds to proteins that support brain cell structure, it also interacts with proteins in charge of vesicles and cell surface receptors for neurotransmitters, which are necessary for learning and memory formation.
“We’re quite aware of the effects of tau protein in dementia-related memory loss but what is interesting to see is that tau helps control normal memory processes,” says study lead author and Flinders University PhD student Emmanuel Prikas.
Building off this, NSF, or N-maleimide sensitive factor, is an enzyme that controls the amount of neurotransmitter receptors that increase during neural synapses in memory formation. This enzyme has been found to be a new partner that interacts with tau, so the researchers used this information to examine how tau contributes to processes involving glutamate, an excitatory neurotransmitter, using microscopy and memory testing with mice.
To further solidify the findings of NSF in cultured brain cells, the researchers removed and restored tau. They noticed that NSF was uncontrolled in cells lacking tau, ultimately leading to abnormal glutamate receptor behavior. This was a valuable finding for the team, since it can possibly help develop targeted therapeutic interventions.
Previously, glutamate and tau have both been connected to seizures in epilepsy and stroke. Therefore, the findings from this work can help give valuable insight into the link between the brain function of tau in controlling glutamate receptors and conditions of increased brain activity. Further, mutations in NSF have been shown to play a role in epilepsy developed hereditarily, allowing this to be studied compared to tau’s role in it as well.
Tau is currently not as well-studied regarding memory loss in the presence of Alzheimer’s disease, say researchers. Now, these findings could be revolutionary for this field of research, and the researchers hope that they serve as solid starts to delving deeper in the connection between normal brains and brains that’ve experienced neurodegeneration.
This study is published in the journal EMBO.