Researchers have developed a novel approach that could someday make it possible to reverse the memory loss caused by Alzheimer’s disease.
The team, led by scientists at the University of Buffalo, discovered that by focusing on genetic changes caused by influences other than DNA sequences, called epigenetic, it was possible to reverse the deterioration of memory in an animal model of Alzheimer’s.
“Not only have we identified the epigenetic factors that contribute to memory loss, but we also found ways to temporarily reverse them in an Alzheimer’s animal model,” said Zhen Yan, a professor at the University of Buffalo in the US. UU
The research, published in the journal Brain, was conducted in mouse models with genetic mutations for familial Alzheimer’s, in which more than one family member has the disease, and in post-mortem brain tissues of Alzheimer’s patients.
Alzheimer’s disease is due to genetic and environmental risk factors, such as aging, that combine to produce epigenetic changes, leading to changes in gene expression, but little is known about how this occurs.
Epigenetic changes in Alzheimer’s disease occur mainly in later stages, when patients can not retain newly learned information and exhibit the most dramatic cognitive decline, Yan said.
A key reason for cognitive decline is the loss of glutamate receptors, which are critical for learning and short-term memory.
The researchers found that the loss of glutamate receptors is the result of an epigenetic process known as repressive histone modification, which is elevated in Alzheimer’s disease.
“Our study not only reveals the correlation between epigenetic changes and Alzheimer’s, we also discovered that we can correct cognitive dysfunction by targeting epigenetic enzymes to restore glutamate receptors,” Yan said.
The Alzheimer animals were injected three times with compounds designed to inhibit the enzyme that controls the repressive modification of histones.
In animals that received the enzyme inhibitor, cognitive function was restored and confirmed by recognition memory assessments, spatial memory and working memory.
The improvements lasted a week. Future studies will focus on developing compounds that penetrate the brain more effectively and, therefore, are more durable, researchers say.