For many, Alzheimer’s disease is just a fact of old age; around 50 percent of people that live to age 85 will get the disorder. It may take years before the characteristic cognitive decline becomes evident, even though the process starts long before that. Researchers have been looking for ways to diagnose the disease sooner or treat it once symptoms appear. Scientists at the University of Virginia have looked at the disorder in a new way, and have found that a drug that's already on the market may help prevent the disease.
The drug, mematine, is now used for people that already have a moderate or severe case of Alzheimer’s. It may, however, also be useful for slowing or stopping the progression of the disease if it’s taken before a person exhibits symptoms of the disease. This study has been reported in Alzheimer's & Dementia.
"Based on what we've learned so far, it is my opinion that we will never be able to cure Alzheimer's disease by treating patients once they become symptomatic," said George Bloom, a UVA professor and chair of the Department of Biology, who oversaw the research in his lab.
"The best hope for conquering this disease is to first recognize patients who are at risk and begin treating them prophylactically with new drugs and perhaps lifestyle adjustments that would reduce the rate at which the silent phase of the disease progresses. Ideally, we would prevent it from starting in the first place."
Most neurons develop before we’re born and then they exit the cell cycle - they stop dividing. But as the disease sets in, neurons in the brain begin to divide again. It may be their way of trying to make up for the neurons that are being lost. In people affected by the disease, the cells try to divide but end up dying.
"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," Bloom explained. "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."
Erin Kodis, a graduate student in the Bloom lab at the time of the work, suggested that the neurons reenter the cell cycle and begin to divide again because of excess calcium that’s getting into the cells. This precedes the formation of amyloid plaques, a well-known feature of Alzheimer's brain; they're composed of a protein called amyloid beta oligomers.
Kodis determined that when toxic amyloid oligomers come into contact with a neuron, it opens the neuron’s NMDA receptors. That allows calcium into the cell and sends the neurons back into the cell cycle. Mematine, however, can close the NMDA receptor.
"The 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," Bloom said. "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."
The drug appears to have few side effects. If potential patients can be identified with biomarker screens, mematine may be able to prevent the disease from taking hold.
"I don't want to raise false hopes," Bloom noted, but "if this idea of using memantine as a prophylactic pans out, it will be because we now understand that calcium is one of the agents that gets the disease started, and we may be able to stop or slow the process if done very early."
The work continues; Bloom and colleagues are planning a clinical trial testing mematine as a preventative medicine.
Check out the video to learn more about recent research on Alzheimer’s disease, and tips on prevention.