Scientists propose new way to repair memory issues caused by Alzheimer’s
There are some new treatments that show promise in slowing the disease that robs people’s memories. But in a new study, researchers are proposing an alternative strategy to reverse the memory problems that come with Alzheimer’s and related dementia.
According to the Buck Institute for Research on Aging, most current research on Alzheimer’s treatments focuses on reducing toxic proteins that accumulate in the brain as the disease progresses. However, the research team that published a study in The Journal of Clinical Investigation took a different course. “Rather than trying to reduce toxic proteins in the brain, we are trying to reverse the damage caused by Alzheimer’s disease to restore memory,” explained Tara Tracy, senior author of the study, in a press statement. Tracy is an assistant professor at Buck.
The new work focuses on a protein called KIBRA, which is found in the kidney and the brain. In the human brain, it is mainly found at the synapses, which are the connections between neurons that enable memory formation and recall. Past research has shown that KIBRA is required for synapses to form memories and the team led by Tracy found that brains with Alzheimer’s are KIBRA deficient.
“We wondered how the lower levels of KIBRA affected signaling at the synapse, and whether understanding that mechanism better could yield some insight into how to repair the synapses damaged during the course of Alzheimer’s disease. What we identified is a mechanism that could be targeted to repair synaptic function, and we are now trying to develop a therapy based on this work,” said Grant Kauwe, co-first author of the study, in a press statement.
They began by measuring KIBRA levels in human cerebrospinal fluid. They found high levels in the cerebrospinal fluid and lower levels in the brain, corresponding with the severity of dementia.
“We also found this amazing correlation between increased tau levels and increased KIBRA levels in the cerebrospinal fluid. It was very surprising how strong the relationship was, which really points to the role of KIBRA being affected by tau in the brain,” added Tracy. Tau is a toxic protein formed in the brain during the disease.
To find out how KIBRA affects synapses, the researchers created a shortened functional version of the protein. After experimenting with lab mice with a condition that mimics Alzheimer’s disease, they found that the protein can reverse the type of memory impairment associated with that type of dementia. KIBRA seemed to be rescuing mechanisms that promote the resilience of synapses.
According to the researchers, this supports the possibility that KIBRA could be used as treatment to improve memory after the onset of Alzheimer’s disease even if the toxic protein that caused the damage is still there.
