Scientists Discover the 'Big Bang' of Alzheimer's Disease

(Credit: UT Southwestern Medical Center/ Screenshot)

Scientists have discovered a “big bang” of Alzheimer’s disease — the precise point at which a healthy protein becomes toxic but has not yet formed deadly tangles in the brain. 

Not only does the study provide novel insight into the shape-shifting nature of tau molecule just before it begins sticking to itself to form larger aggregates; The revelation also offers a  new strategy to detect the devastating disease before it takes hold, and has spawned an effort to develop treatments that stabilise tau proteins before they shift shape.

 

“We think of this as the big bang of tau pathology.” 

 

The study, published in eLife, contradicts the previous belief that an isolated tau protein has no distinct shape and is only harmful after it begins to assemble with other tau proteins to form the distinct tangles seen in the brains of Alzheimer’s patients. 

Scientists made the discovery after extracting tau proteins from brains and isolating them as single molecules. They found that the harmful tau exposes a part of itself that is normally folded inside. 

This exposed portion causes it to stick to other tau proteins, enabling the formation if tangles that kill neurons. 

“We think of this as the big bang of tau pathology,” said Dr. Mark Diamond, Director for UT Southwestern’s Center for Alzheimer’s and Neurodegenerative Diseases, referring to the prevailing scientific theory about the formation of the universe. 

“This is a way of peering to the very beginning of the disease process. It moves us back to a very discreet point where we see the appearance of the first molecular change that leads to neurodegeneration in Alzheimer’s.”

Scientists Discover the 'Big Bang' of Alzheimer's Disease

Abnormal accumulations of a protein called tau can collect inside neurons, forming tangled threads and eventually harming the synaptic connection between neurons. (Credit: National Institute of Aging)

Diamond is hopeful the scientific field has turned a corner, noting that identifying the genesis of the disease provides scientists with a vital target in diagnosing the condition at its earliest stage, before the symptoms of memory loss and cognitive decline become apparent. 

The next step for Diamond and his team is to develop a clinical test that examines a patient’s blood or spinal fluid to detect the first biological signs of the abnormal tau protein. But just as important, Diamond said, efforts are underway to develop a treatment that would make the diagnosis actionable. 

He cites a compelling reason for cautious optimism: Tafamidis, a recently approved drug, stabilises a different shape-shifting protein called transthyretin that causes deadly protein accumulation in the heart, similar to how tau overwhelms the brain. 

“The hunt is on to build on this finding and make a treatment that blocks the neurodegeneration process where it begins,” he said. 

“If it works, the incidence of Alzheimer’s disease could be substantially reduced. That would be amazing.” 

 


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