New approach offers hope for regaining memories lost in Alzheimer's disease

A newly approved treatment for Alzheimer's disease holds promise for slowing the progression of the memory-robbing disease, but current treatments are far from effective in restoring memory. What is needed is more treatment options aimed at restoring memory, said Buck Assistant Professor Dr. Tara Tracy. He is the lead author of a study proposing alternative strategies to improve memory impairment associated with Alzheimer's disease and related dementias.

Most current research into potential treatments for Alzheimer's disease focuses on reducing toxic proteins such as tau and amyloid beta, which accumulate in the brain as the disease progresses, so the research team I deviated from the route and looked for an alternative. “Rather than trying to reduce toxic proteins in the brain, we are trying to reverse the damage caused by Alzheimer's disease and restore memory,” Tracy said. The results of this survey will be published in the February 1 issue. clinical research journal.

The research relies on a protein called KIBRA, named for its presence in the kidneys and brain. In the brain, it is primarily localized at synapses, the connections between neurons that allow memory formation and recall. Research has shown that KIBRA is required for synapses to form memories, and Tracy's team found that brains with Alzheimer's disease are deficient in KIBRA.

We hope that a deeper understanding of how reduced KIBRA levels affect synaptic signaling and its mechanisms may provide some insight into how to repair damaged synapses during the course of Alzheimer's disease. I thought I might get it. What we have identified is a mechanism that can be targeted to repair synaptic function, and we are currently trying to develop treatments based on this research. ”

Dr. Grant Cowe, study co-lead author and back staff scientist

The research team first measured KIBRA levels in human cerebrospinal fluid. They found that high KIBRA levels in the cerebrospinal fluid but low KIBRA levels in the brain corresponded to the severity of dementia.

“We also found a surprising correlation between increased tau levels and increased KIBRA levels in the cerebrospinal fluid,” Tracy said. “We were very surprised by how strong this relationship was. This really points to the role of KIBRA, which is influenced by tau in the brain.” and are investigating this phenomenon further in the hope that it can be used as a biomarker of synaptic dysfunction and cognitive decline that may help track response to treatment.

To understand how KIBRA affects synapses, the researchers created a functionally truncated version of the KIBRA protein. Using laboratory mice with symptoms that mimic Alzheimer's disease in humans, they discovered that the protein could reverse the memory deficits associated with this type of dementia. They found that KIBRA rescues mechanisms that promote synaptic resilience.

“Interestingly, KIBRA restored synaptic function and memory in mice, even though it did not solve the problem of toxic tau protein accumulation,” said Christine, co-lead author of the study. Pareja Navarro said. “Our study supports the possibility that KIBRA can be used as a therapy to improve memory after the onset of memory loss, even though the toxic proteins that caused the memory loss remain.”

Like other treatments that already exist or will be introduced in the future, KIBRA therapy to repair synapses could be a valuable addition. “Reducing toxic proteins is of course important, but repairing synapses and improving their function is also an important element that may help,” Tracy said. “I see this as having the biggest impact going forward.”