Now, a new study has found that brain immune cells called microglia -- which are activated as tau tangles accumulate -- form the crucial link between protein clumping and brain damage. The research, published Oct. 10 in the Journal of Experimental Medicine, shows that eliminating such cells sharply reduces tau-linked brain damage in the mice -- and suggests that suppressing such cells might prevent or delay the onset of dementia in people.
"Right now many people are trying to develop new therapies for Alzheimer's disease, because the ones we have are simply not effective," said senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. "If we could find a drug that specifically deactivates the microglia just at the beginning of the neurodegeneration phase of the disease, it would absolutely be worth evaluating in people."
Circumstances - Tau - Contributes - Functioning - Brain
Under ordinary circumstances, tau contributes to the normal, healthy functioning of brain neurons. In some people, though, it collects into toxic tangles that are a hallmark of neurodegenerative diseases such as Alzheimer's and chronic traumatic encephalopathy, a progressive brain disease often diagnosed in football players and boxers who have sustained repeated blows to the head. Holtzman and colleagues previously had shown that microglia limit the development of a harmful form of tau. But the researchers also suspected that microglial cells could be a double-edged sword. Later in the course of the disease, once the tau tangles have formed, the cells' attempts to attack the tangles might harm nearby neurons and contribute to neurodegeneration.
To understand the role of microglial cells in tau-driven neurodegeneration, Holtzman, first author and postdoctoral researcher Yang Shi, PhD, and colleagues studied genetically modified mice that carry a mutant form of human tau that easily clumps together. Typically, such mice start developing tau tangles at...
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