Dementia is one of the most debilitating consequences of Parkinson’s disease, a progressive neurological condition characterized by tremors, stiffness, slow movement and impaired balance. Eighty percent of people with Parkinson’s develop dementia within 20 years of the diagnosis, and patients who carry a particular variant of the gene APOE are at especially high risk.
In new research, scientists at Washington University School of Medicine in St. Louis have found a clue to the link between Parkinson’s, APOE and dementia. They discovered that harmful Parkinson’s proteins spread more rapidly through the brains of mice that have the high-risk variant of APOE, and that memory and thinking skills deteriorate faster in people with Parkinson’s who carry the variant. The findings, published Feb. 5 in Science Translational Medicine, could lead to therapies targeting APOE to slow or prevent cognitive decline in people with Parkinson’s.
“Dementia takes a huge toll on people with Parkinson’s and their caregivers,” said Albert (Gus) Davis, MD, PhD, an assistant professor of neurology and the study’s lead author. “The development of dementia is often what determines whether someone with Parkinson’s is able to remain in their home or has to go into a nursing home.”
An estimated 930,000 people in the U.S. live with Parkinson’s. The disease is thought to be caused by toxic clumps of a protein called alpha-synuclein that build up in a part of the brain devoted to movement. The clumps damage and can kill brain cells.
Cognitive problems tend to arise many years after the motor symptoms. The protein clusters implicated in movement problems also are linked with dementia, but how this happens is not clear. Davis and his colleagues – including senior author David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology – saw a clue in the risky nature of APOE.