UF Neuroscientists Demonstrate a Link Between Parkinson’s and Alzheimer’s Disease
Oct 23, 2013 - 10:37:21 AM
"Until now, nobody has really understood what the overlap between Alzheimer's and Parkinson's disease was, or if it were important," said Jada Lewis, Ph.D., an associate professor of neuroscience in the Center for Translational Research in Neurodegenerative Disease. "Our study ties these diseases together in a unique way."
Lewis and her colleagues, UF graduate student Rachel M. Bailey, UF associate professor Benoit Giasson, and Jason P. Covy of Stanford University, reported their findings in the journal Acta Neuropathologica.
The scientists focused their research on a protein called tau. Tau is a normal and useful protein in the brain and its function is controlled by the addition of phosphate groups. However, this protein becomes abnormally phosphorylated and forms clumps or "tangles" in diseased brains. Tangles are associated with cognitive impairment in some neurodegenerative diseases, including Alzheimer's disease, about 20 percent of Parkinson's patients and a host of diseases lumped together under the moniker "tauopathies."
One culprit behind familial Parkinson's disease is a mutated form of an enzyme known as LRRK2, pronounced "lerk two." Parkinson's patients who have this mutation can form the problematic tangles of tau protein.
Through a series of studies, they found that normal LRRK2 adds phosphate groups to tau protein and mutated LRRK2 adds many more phosphate groups to tau protein than normal LRRK2. Using the data from these studies, they identified two largely unexplored sites on the tau protein where mutated LRRK2 added phosphate groups, and this was associated with the increased formation of tangles. Importantly, Lewis and her colleagues then evaluated their findings in brain tissue from humans and found that the two tau sites targeted by LRRK2 in the laboratory setting also are altered in humans with the LRRK2 mutation. Additionally, these same changes were found in human brains affected by Alzheimer's disease and a number of other diseases that form tangles.
"Together our studies provide evidence that LRRK2 and tau interact in human disease and provide new therapeutic targets for both Alzheimer's and Parkinson's disease," Bailey said.
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