You may not be familiar with neurons and what they do in the brain, but they play an important role in the organ and the nervous system at large.
The cells are “responsible for receiving sensory input from the external world, for sending motor commands to our muscles, and for transforming and relaying the electrical signals at every step in between,” according to The University of Queensland’s Alan Woodruff. Ph.D., who wrote about neurons on the school’s Queensland Brain Institute website.
For a person with Alzheimer’s disease, neurons degenerate and die. When they do, memories and cognitive skills are slowly removed. But not all neurons are affected in the same way. While some of them die, others do not.
A new study from Gladstone Institutes shows why that is.
Researchers from the independent San Francisco Bay Area-based nonprofit life science research organization have found a link between neurons with high rates of a particular protein and rates of degeneration. High rates of the protein apolipoprotein E (apoE) mean these neurons are more susceptible to degeneration. The susceptibility is tied to apoE’s regulation of neurons’ immune-response molecules.
The findings were published Thursday in the journal Nature Neuroscience.
“This is the first time such a link has been established, which is quite exciting and could open new paths to developing treatments for Alzheimer’s disease,” senior author and Gladstone Senior Investigator Dr. Yadong Huang said in a press release.
The team used recent developments in single-cell analysis to study the possible role apoE plays in Alzheimer’s disease. More specifically, investigators looked into how the protein affects the shifting susceptibility of neurons. With a technique called single-nucleus RNA sequencing, scientists could compare individual cells. They could do so inside a certain type of cell and in a range of varying cell types.
In a study of mice, Gladstone researchers analyzed the brain tissue from healthy rodents and mouse models of Alzheimer’s disease. Additionally, they evaluated publicly available data for human brain tissue. This data included some from healthy brains and others with differing stages of Alzheimer’s disease or mild cognitive impairment.
Both analyses showed the extent of apoE expression varied widely in neurons. This was even the case within the same subtype. The levels of apoE expression was also heavily tied to the expression of immune-response genes. That factor also had notable fluctuations among neurons.
The team also discovered that high levels of apoE turned on genes in the major histocompatibility complex class-I (MHC-I). This is part of a pathway involved in removing excess connections between neurons called synapses in brain development. In the adult brain, MHC-I may also alert the immune system to damaged neurons and synapses.
Huang, who is also the director of the Center for Translational Advancement at Gladstone, as well as a professor of neurology and pathology at the University of California, San Francisco, summed up the findings in this way.
“We think that, normally, apoE turns on the expression of MHC-I in a small number of damaged neurons to produce ‘eat me’ signals that mark the neurons for destruction by the immune cells,” Huang said. “You don’t want to keep damaged neurons around because they could malfunction and cause problems.”
For more on the study, view the press release here.
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