A rare gene change known to delay Alzheimer’s also curbed Parkinson’s-type protein clumps in mice, Oregon researchers report
The Christchurch version of the APOE gene could point toward a gene therapy for Parkinson’s and Lewy body dementia, but any human test is years away.
A rare gene change that seems to protect some people from Alzheimer’s disease also slowed the buildup of the protein clumps seen in Parkinson’s disease in mice, according to a study from Oregon Health & Science University published this week in the journal Cell Reports. The researchers say the finding could lead to a gene therapy for Parkinson’s and Lewy body dementia, though testing in people would take years.
The change, called the Christchurch mutation after the New Zealand city where it was first found, is in APOE, a gene that makes a protein that carries fats and cholesterol. Interest in it grew after a 2019 report on a woman in Colombia who carried it and stayed free of dementia decades longer than expected, despite inheriting a gene that almost always causes early Alzheimer’s, the university said.
What the researchers found
- In mice with the mutation, clumps of alpha-synuclein, the protein that builds up in Parkinson’s and Lewy body dementia, formed less and spread less through the brain. Clumps also spread less from a leg muscle to the spinal cord.
- The mutated APOE protein bound alpha-synuclein more tightly than the normal version.
- In mice bred to develop Alzheimer’s-like amyloid plaques and then injected with tau from Alzheimer’s brains, the mutation reduced amyloid and the tangled tau the plaques help trigger. It did not change plaques or tau in mice that were not injected.
- Mice with the mutation had higher blood cholesterol and triglycerides, as seen in people who carry it.
The team used gene editing to put the mouse version of the mutation into mice, then bred them with mice prone to these brain diseases or injected clumped proteins to start the disease process. “It opens up this idea that this Christchurch mutation could be helpful for a lot of things we didn’t realize before,” said senior author Vivek Unni, an associate professor of neurology. Mouse results often do not carry over to people.