Almost 80 per cent of people with Parkinson’s disease, a progressive neurological condition characterised by tremors, slow movement, and impaired balance, will develop dementia within 20 years.
Now, researchers at Washington University have discovered that those who carry a certain variant of the gene APOE may be especially at risk, potentially opening doors to treatments to slow or prevent cognitive design in people with Parkinson’s.
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Parkinson’s is thought to be caused by toxic clumps of a protein called alpha-synuclein that build up in a part of the brain involved with coordinating movement. These clumps damage and can kill brain cells, and are also linked with the onset of dementia.
“Dementia takes a huge toll on people with Parkinson’s and their caregivers,” said the study’s lead author Assistant Professor Albert (Gus) Davis. “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.”
Like Parkinson’s, Alzheimer’s is also caused by the spread of toxic protein clusters throughout the brain. It was previously known that a variant of the APOE gene known as APOE4 raises the risk of Alzheimer’s disease in humans by up to five times, partly because it spurs proteins to collect into clumps that injure the brain.
The researchers suspected that APOE4 would produce a similar effect in triggering the growth of toxic clusters of Parkinson’s proteins. To test this, they genetically modified mice to carry different variants of the APOE gene. They found that mice with the APOE4 gene variant had more alpha-synuclein protein clusters than those with other variants or no copy of the gene at all.
“Parkinson’s is the most common, but there are other, rarer diseases that also are caused by alpha-synuclein aggregation and also have very limited treatment options,” said Assistant Professor Davis said. “Targeting APOE with therapeutics might be a way to change the course of such diseases.
“APOE doesn’t affect the overall risk of developing Parkinson’s or how quickly movement symptoms worsen, so an APOE-targeted therapy might stave off dementia without doing anything for the other symptoms.”
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