Mouse APOE Christchurch protects against Aβ-induced tau and α-synuclein aggregation.

APOE Christchurch knock-in mice show reduced Aβ-induced tau pathology and decreased formation and spread of α-synuclein aggregation, including peripheral-to-spinal cord spread.

• Why it matters: APOE genotype shapes dementia risk across Alzheimer’s disease, Parkinson’s disease, and dementia with Lewy bodies, but APOE Christchurch effects in PD/DLB-related pathology were unknown.
• What they did: The team generated APOE CC knock-in mice and tested Aβ and Aβ-induced tau after intracortical AD-tau injection into 5xFAD mice, while also assessing α-syn aggregation and spread in brain and peripheral-to-spinal cord pathways.
• The result: APOE CC increased plasma cholesterol and triglycerides, lowered Aβ and Aβ-induced tau pathology in the injected 5xFAD context, and reduced α-syn aggregation and spread while directly increasing α-syn binding affinity versus APOE WT.

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