Yale researchers made the discovery in a new scientific study

Mar 19, 2014 14:36 GMT  ·  By
Senile plaques seen in the cerebral cortex in a patient with Alzheimer disease
   Senile plaques seen in the cerebral cortex in a patient with Alzheimer disease

A group of scientists based at the Yale University argues in a new scientific paper that the molecular changes that lead to neurofibrillary tangles in the human brain may originate in highly-evolved brain circuits affected by old age. These tangles are one of the hallmarks associated with Alzheimer's disease, a neurodegenerative form of dementia that represents a worsening public health problem globally.

In a paper published in the March 17 issue of the esteemed journal Proceedings of the National Academy of Sciences (PNAS), the Yale group reveals that old age makes these circuits more likely to experience the type of errors that lead to the development of such tangles. The latter are structures containing a hyperphosphorylated version of the tau protein, the primary Alzheimer's marker.

Despite the fact that neurofibrillary tangles (NFT) have come under intense scrutiny over the past few years, researchers still do not know how these structures assemble. Studies have also failed to properly clarify if they play a central role in the development of dementia or are simply associated with it. What researchers do know is that old age is a significant risk factor for both NFT and Alzheimer's.

The new results may also go a long way towards explaining why the sensory cortex remains largely unaffected by neurodegenerative dementia, while more advanced circuitry underlying cognition and other higher aspects of the brain are so vulnerable. Scientists agree that discovering the molecular agents underlying this difference will be key to addressing this disorder.

“We hope that understanding the key molecular alterations that occur with advancing age can provide new strategies for disease prevention,” says senior study co-author Amy F.T. Arnsten, who is a professor of neurobiology at the university. The other members of the study team are researchers Becky C. Carlyle, Angus Nairn, and Constantinos D. Paspalas, all from Yale.

“This insight into one pathway by which tau may influence the onset and progression of Alzheimer’s disease takes us a step closer to unraveling this complex and devastating disorder,” explains US National Institutes of Health expert Dr. Molly Wagster. NIH partially supported this research.

The team explains that tau proteins exist naturally in the brain and that they do not usually cause trouble. Before the onset of dementia, their structure is modified through a process called phosphorylation, which makes the molecules sticky and more likely to clump up together. Hyperphosphorylated tau proteins are extremely likely to form NFT.

Most often, these modified proteins start to clump up around synapses between neurons in higher brain circuits. “Now that we begin to see what makes neurons vulnerable, we may be able to protect cells with treatments that mimic the protective effects of [naturally-occurring enzymes in the young brain],” Arnsten says.