Georgetown researchers discover new Alzheimer’s physiology and propose potential treatment paths
In a new study published on Oct. 31 in the journal Molecular Neurodegeneration, a team of neuroscientists at the Georgetown University Medical Center overturned a widely-accepted theory regarding the physiology of Alzheimer’s disease and opened a new path for potential treatment options.
Alzheimer’s disease is a form of dementia whose biological signs include amyloid-beta plaque and neurofibrillary tangle formation in the brain, ultimately leading to neuronal death. By the time symptoms such as memory loss appear in a patient, the disease has already advanced without hope of recourse.
Alzheimer’s disease is the sixth leading cause of death in the United States. Over 5 million Americans have Alzheimer’s disease, and that number will likely increase to 16 million by 2050 if treatment options are not discovered. Deaths from Alzheimer’s disease increased 68 percent between 2000 and 2010.
Up to this point, scientists have attributed brain cell death to amyloid-beta plaques, extracellular protein deposits in the brains of Alzheimer’s disease patients. In this new study headed by Charbel Moussa, assistant professor and head of the Laboratory for Dementia and Parkinsonism, the authors found evidence that intracellular plaque build-up due to defective protein tau, not extracellular amyloid-beta, largely contributes to neuronal death in Alzheimer’s disease.
Tau is a protein that regulates transport machinery in cells. This study investigated how tau may help the cell in clearing amyloid-beta deposits from its cytoplasm. In their experiment, researchers successfully deleted the tau gene, impairing amyloid-beta clearance from the cell.
When tau was introduced to mice genetically engineered to be unable to produce their own tau, the animals partially regained the ability to clear amyloid-beta.
The study also investigated the effect of the cancer drug Nilotinib on amyloid-beta build-up. Nilotinib is known to promote cellular clearance mechanisms. When this drug was delivered to non-tau-producing mice, cells were able to clear amyloid-beta in the presence of external tau.
Researchers had long been puzzled by diseases characterized by defective tau and no plaque growth. This new study not only explains why this might be the case, but also proposes a potential treatment option.
“There are many diseases of dementia that have malfunctioning tau and no plaque accumulation, such as frontal temporal dementia linked to Parkinsonism,” Moussa said in a press release. “The common culprit is tau, so a drug that helps tau do its job may help protect against progression of these diseases.”
Photo: Georgetown University