Scientists developed a new test in mice that can identify Alzheimer's symptoms at a young age, providing a new detection channel for early intervention.
Researchers may now be able to predict memory problems far in advance by identifying certain brain activity patterns. In a new study out of Gladstone Institutes, scientists tested this new method in mice with the goal of identifying Alzheimer’s memory loss sooner—so interventions can be established as quickly as possible.
“Being able to predict [memory] deficits long before they appear could open up new opportunities to design and test interventions that prevent Alzheimer’s in people,” Yadong Huang, Gladstone Senior Investigator and an author of the study, said in a news release.
The study, published in Cell Reports, relied on research from a previous study on the APOE4 gene. The APOE4, or apolipoprotein E4, gene has been the subject of numerous recent investigations to better understand its role in neurodegenerative diseases. If someone carries the APOE4 gene, they have a much higher chance of developing Alzheimer’s disease.
In the most recent development on APOE4, scientists discovered that a woman carrying the APOE4 gene also had a genetic mutation that caused a delay in the disease developing in her. While the gene she carried highly increased her risk of developing Alzheimer’s in her 30s, she didn’t develop it until her 70s.
Other recent research out of the Banner Alzheimer’s Institute picked apart different types of the APOE gene and their varying impacts on Alzheimer’s risk.
In the previous Gladstone study, the researchers examined sharp-wave ripples (SRWs), a type of brain pattern involved in spatial learning and memory in mammals. In aging mice that carried the APOE4 gene—meaning they had a higher risk of developing Alzheimer’s—the researchers noticed SRWs were weaker compared to healthy aging mice. Impaired SRWs are associated with worsened memory and spatial learning.
In the latest study, they decided to test whether identifying weak SRWs in advance could help predict Alzheimer’s disease.
“We actually successfully replicated this experiment two years later with different mice,” Huang said. “What was striking is that we were able to use the results from the first cohort to predict with high accuracy the extent of learning and memory deficits in the second cohort, based on their SWR activity.”
Predicting Alzheimer’s memory loss early on
Taking the investigation one step further, the researchers also wanted to test whether it was possible to predict memory problems based on SRW activity at a young age.
They found that impaired SRWs at an early age could predict whether mice would have memory problems later on.
“We were not betting on these results, the idea that young mice with no memory problems already have the seed of what’s going to lead to deficits in old age,” Emily Jones, lead author of the study, said in the news release. “Although we would love to, but we thought it would be ridiculous to be able to predict so far in advance.”
The next step is to test the research in humans. The researchers hypothesize that testing SRW activity in humans at an early age could predict memory loss from Alzheimer’s years down the road. In the next study at UCSF Memory and Aging Center, Huang aims to test SRWs in Alzheimer’s patients to see if weaker signals are linked to memory loss.
“I feel strongly that Alzheimer’s research should not just focus on pathology, but use functional alterations like SWR deficits to guide research and drug development,” Huang said.
Currently, the only way to properly diagnose Alzheimer’s disease is after death, during an autopsy of the brain. However, doctors are pushing for earlier detection to improve interventions and treatments.
Memory and neurological tests can help identify what patients likely have dementia, but these are often carried out long after a person begins showing symptoms. Being able to detect Alzheimer’s risk far in advance, whether through the APOE gene or SRW patterns, could help doctors start treatment or preventive approaches earlier on.