A rare genetic mutation prevents the brain from accumulating proteins that drive Parkinson’s disease and Lewy body dementia, a study published in Cell Reports shows.
Researchers at Oregon Health & Science University examined the Christchurch mutation of the APOE gene in a rodent model. Previous research beginning in 2019 showed that this rare mutation, first discovered in New Zealand, forestalls dementia symptoms in individuals genetically destined to develop Alzheimer’s disease.
The new study confirms the mutation prevents the accumulation of the Alzheimer’s-related tau protein.
Researchers demonstrated that the mutation stops the buildup of alpha-synuclein, a protein characteristic of Parkinson's disease progression and Lewy body dementia.
“It opens up this idea that this Christchurch mutation could be helpful for a lot of things we didn’t realize before,” said Vivek Unni, M.D., Ph.D., senior author and associate professor of neurology at the OHSU School of Medicine, News-Medical reported.
OHSU scientists utilized mouse models genetically predisposed to accumulate both alpha-synuclein and tau proteins in the brain. They introduced the Christchurch mutation into the APOE gene to observe the physiological results. Mice carrying the mutation failed to accumulate tau or alpha-synuclein proteins despite their underlying genetic predisposition.
Gene therapies currently under development use another variant of the APOE gene, known as APOE-2, which also offers protection against Alzheimer's disease. Unni said that the Christchurch variant provides even stronger defense.
“[It] acts like a super-APOE-2,” Unni told News-Medical, describing its efficacy in the examined mouse model.
Unni’s laboratory is actively seeking grant funding to extend preclinical research on the Christchurch mutation. The extended timeline aims to secure enough evidence to convince pharmaceutical companies to invest in human clinical trials for APOE Christchurch gene therapies.
“It would take several years to test the idea,” Unni told News-Medical.
The initial research phase received funding awards from the Oregon Alzheimer’s Disease Research Center, the Parkinson Center at OHSU, the American Parkinson Disease Association, and the nonprofit organization Stop Alzheimer’s Now. Co-authors on the published paper include Carlos Soto-Faguas, Abigail O’Niel, Elizabeth Saltonstall, Paul Mueller, Paula Sanchez-Molina, Lev Fedorov, Randall Woltjer, and Jacob Raber.
- Journal Reference: Published in Cell Reports under DOI 10.1016/j.celrep.2026.118301.
- Target Proteins: The mutation blocks both tau and alpha-synuclein accumulation.
- Lead Institution: Oregon Health & Science University.
The Christchurch mutation is a rare genetic alteration of the APOE gene originally discovered in New Zealand. It was initially linked to delaying symptom onset in individuals carrying genes for early-onset Alzheimer’s disease.
In transgenic mouse models predisposed to brain disease, the mutation halts the aggregation of alpha-synuclein and tau proteins. These specific protein accumulations are the primary drivers of neurodegeneration in Parkinson’s disease and Lewy body dementia.
Researchers have not scheduled human clinical trials yet. Investigators must first secure additional grant funding to complete required preclinical testing phases before pharmaceutical companies can advance the gene therapy toward human testing.
Keep reading