A rare genetic variation tied to the APOE gene may shield individuals from both Parkinson’s disease and Lewy body dementia, according to new findings from Oregon Health & Science University researchers. The study, published in Cell Reports, identifies the so-called Christchurch mutation as a potential disruptor of toxic protein buildup in the brain—a key factor in both conditions.
This work builds on previous research involving a Colombian woman who carried the mutation and exhibited delayed dementia symptoms despite a genetic risk for Alzheimer’s. Earlier investigations had centered on tau protein, which is linked to Alzheimer’s. The OHSU team, however, examined the mutation in mice prone to accumulating alpha-synuclein, the protein tied to Parkinson’s and Lewy body dementia.
In every tested case, mice with the Christchurch mutation avoided harmful protein deposits, even when genetically predisposed to them. The mutation appears to prevent the accumulation of both tau and alpha-synuclein, indicating a broader protective role than previously understood. Unlike other APOE variants, such as APOE-2, which also provides some protection, the Christchurch mutation demonstrated stronger effects in animal models.
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Researchers had already observed the mutation’s ability to block tau aggregation in Alzheimer’s, but this study marks the first extension of those results to Parkinson’s-related proteins. The team now seeks funding for further preclinical trials, with the long-term goal of developing gene therapy based on the mutation’s mechanisms.
While gene therapies targeting APOE-2 are already under development for Alzheimer’s, the Christchurch mutation’s superior performance in mice could position it as a more effective option. Vivek Unni, lead author and associate professor of neurology, described the mutation as functioning like a “super-APOE-2,” though human trials would require extensive testing before pharmaceutical investment.
