In a recent study, researchers found that an FDA-approved drug, memantine, may be used to prevent or slow the progression of the disease if used before symptoms appear.
This drug is currently used only for alleviating the symptoms of moderate-to-severe Alzheimer’s disease.
The research is from the University of Virginia.
About 50% of people who reach the age of 85 will develop Alzheimer’s disease.
Most will die within about five years of exhibiting the hallmark symptoms of the disease – severe memory loss and a precipitous decline in cognitive function.
But the molecular processes that lead to the disease will have begun years earlier.
This study offers new understanding of how the disease develops at the molecular level, long before extensive neuronal damage occurs and symptoms show up.
The research also offers, based on extensive experimentation, a hypothesis as to why early use of the drug may help stop the disease.
As Alzheimer’s disease begins, there is a lengthy period of time, perhaps a decade or longer, when brain neurons affected by the disease attempt to divide, possibly as a way to compensate for the death of neurons.
This is unusual in that most neurons develop prenatally and then never divide again. But in Alzheimer’s the cells make the attempt, and then die.
It’s been estimated that as much as 90 percent of neuron death that occurs in the Alzheimer’s brain follows this cell cycle reentry process, which is an abnormal attempt to divide.
By the end of the course of the disease, the patient will have lost about 30 percent of the neurons in the frontal lobes of the brain.
The team hypothesized that excess calcium entering neurons through calcium channels on their surface drive those neurons back into the cell cycle.
This occurs before a chain of events that ultimately produce the plaques found in the Alzheimer’s brain. Several experiments by Kodis ultimately proved her theory correct.
The building blocks of the plaques are a protein called amyloid beta oligomers.
The team found that when neurons are exposed to toxic amyloid oligomers, the channel, called the NMDA receptor, opens, thus allowing the calcium flow that drives neurons back into the cell cycle.
The drug Memantine could block cell cycle reentry by closing the NMDA receptor.
Their experiments suggest that memantine might have potent disease-modifying properties if it could be administered to patients long before they have become symptomatic and diagnosed with Alzheimer’s disease.
Perhaps this could prevent the disease or slow its progression long enough that the average age of symptom onset could be significantly later, if it happens at all.
Side effects of the drug appear to be infrequent and modest.
The researchers said potential patients would need to be screened for Alzheimer’s biomarkers years before symptoms appear.
Selected patients then would need to be treated with memantine, possibly for life, in hopes of stopping the disease from ever developing, or further developing.
The researchers suggest that if this idea of using memantine as a prophylactic pans out, it will be because they now understand that calcium is one of the agents that gets the disease started.
George Bloom, a UVA professor and chair of the Department of Biology, oversaw the study in his lab.
The findings are published in the journal Alzheimer’s & Dementia.
Copyright © 2018 Knowridge Science Report. All rights reserved.
Source: Alzheimer’s & Dementia.