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Unlocking the Secrets of Alzheimer’s Disease

Hall’s Research Shows How Key Protein May Spread in Brain

Garth Hall


Edwin L. Aguirre

A team of researchers led by Dr. Garth Hall, an associate professor in biology at UMass Lowell, has found a new mechanism by which tau - a key protein associated with Alzheimer’s disease - can spread within the human brain. Their work has also provided a new explanation of how tau can appear in the blood and cerebrospinal fluid (CSF) of Alzheimer’s patients, giving new hope that this disease may someday be cured.

Hall, who has spent the better part of 20 years studying Alzheimer’s on the cellular level using larval sea lampreys as a model system, says that his team has discovered two different ways in which tau, a normal human protein that becomes toxic in Alzheimer’s disease, is secreted by neurons, or brain cells. He says this might explain how tau-containing lesions seem to propagate between adjacent, interconnected parts of the brain during the development of the disease. Up until very recently, it has been universally assumed by scientists that tau is never secreted or transferred between neurons at all, and that CSF-tau only appears after many neurons have died and irreversible harm has been done to the brain.

“The fact that tau secretion can occur via two distinct mechanisms strongly indicates that it is biologically ‘real’ and is not just tau protein leaking out of dead neurons,” says Hall. “The fact that it occurs in a pattern that reproduces what is seen in the CSF of Alzheimer’s patients holds out hope that patients in early stages of the disease might someday be cured.”

He adds, “If we can distinguish secreted tau from tau that is released from dying neurons in CSF samples, then maybe we can diagnose Alzheimer’s in time to stop the disease before the neurons die.”

Hall, together with graduate student WonHee Kim and UMass Lowell, has filed a provisional patent application in connection with a novel approach to the early diagnosis of Alzheimer’s that is based on their studies of tau secretion.

Alzheimer’s is the most common form of dementia. It’s a degenerative and terminal brain disorder that typically afflicts people older than 60 years, seriously diminishing their memory, thinking and ability to carry out daily activities and placing great burden on their families and caregivers. So far, there is no known cure for Alzheimer’s.

According to the Alzheimer’s Association, as many as 5.3 million people in the United States are living with the disease. It is the seventh leading cause of death among seniors. “The direct and indirect costs of Alzheimer’s and other dementias to Medicare, Medicaid and businesses amount to more than $148 billion each year,” the association’s website reports.

Alzheimer’s is considered a tauopathy (disorder involving tau) due to the abnormal aggregation of tau protein. Tau develops tangled neurofibrillary filaments or threads that result first in malfunctions in biochemical communications between the neurons and later, in the death of these brain cells. By injecting human tau directly into the lampreys’ brain, Hall and his team were able to replicate tau-induced breakdown of the neurons and show how tau-containing lesions are secreted and transferred between neurons and the surrounding cell spaces. They also showed that the same process occurred in human neuronal cell lines in culture.

The team described their findings this February in Volume 19, Issue 2 of the Journal of Alzheimer’s Disease, an international multidisciplinary publication that aims to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease.

Hall’s team includes three graduate students, four undergraduate students and a postdoctoral fellow in the Center for Cellular Neuroscience and Neurodegeneration Research in the Biology Department at UMass Lowell. Kim and post-doctoral student Sangmook Lee were co-authors of the paper, as was Prof. Gloria Lee of the University of Iowa’s Carver College of Medicine, who has been a longtime collaborator with Hall.

“Our results ... provide a novel conceptual and experimental basis for studying the mechanisms of interneural propagation and toxicity in human neurogenerative disease,” the team wrote in the paper.

WonHee Kim