A group of researchers at UNC Chapel Hill has discovered why one Alzheimer’s drug currently in development shows promise and how other therapies might reverse the disease process.
The researchers, working with mice, found a link between inflamed immune cells in Alzheimer’s brains and a harmful protein that also is present in the brain. They showed neurons developed abnormal, bead-like swellings under these conditions, which is classically seen in the brains of Alzheimer’s victims.
Drug companies are developing and testing a drug that inhibits the interactions between immune cells in the brain and the harmful protein.
“We think that preventing these structures from forming would leave people with healthier neurons that are more resistant to Alzheimer’s,” said Todd Cohen, Ph.D., who led the research at the UNC Neuroscience Center.
Neuritic beading is considered an early sign of neuronal damage. But it hasn’t been clear how or if the beading led to Alzheimer’s disease, according to researchers.
Cohen’s lab also found high calcium levels, which are known to harm neurons and are considered an important feature of neurons in people with Alzheimer’s.
“We think these neuroinflammatory factors trigger this cascade,” Cohen said. “They flood the neuron with calcium. And we think that once the calcium accumulates, it causes abnormal modifications. This probably leads to a snowball effect.”
Both of these factors have been found in affected areas of Alzheimer’s brains.
Neuritic beading is seen in several other neurodegenerative diseases as well as after head injury. Scientists have observed beading to small extents in healthy elderly brains. So beading might be a general mechanism underlying cognitive decline, Cohen said.
The researchers now are focused on creating a mouse model to confirm and further investigate the inflammation process seen in this study.
“If we can demonstrate this cascade in a wild-type mouse, then we’ll be able to study Alzheimer’s and test therapies in ordinary lab mice without the need for traditional Alzheimer’s mouse models,” Cohen said.
Cohen collaborated with three other UNC labs led by Rick Meeker, Ph.D., Xian Chen, Ph.D., and Cohen, as well as the NIH lab of Jau-Shyong Hong, Ph.D.
The project was supported by UNC and the National Institutes of Health.