| Title: | Does homozygous Christchurch mutation in apoE3 delay onset of Alzheimer's disease |
| Lead Institution: | Fermata Pharma, Inc |
| Principal investigator: | Dr Steven Lehrer |
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Scientific rationale: a Colombian woman inherited the autosomal-dominant E280A mutation in presenilin 1 but stayed cognitively well for decades past this mutation's typical age of disease onset. Called Paisa, this mutation causes A! overproduction, triggering neurodegeneration and cognitive decline by a person's 40s. Yet this woman stayed alert for three decades after that. Now in her 70s, she struggles with short-term memory but still remains independent. Amyloid PET scanning revealed a massive buildup of amyloid plaques in her brain, far higher than those seen in young mutation carriers who are cognitively impaired. Despite all this amyloid, she has very little tau pathology, mostly confined to the medial temporal lobe, and her brain glucose metabolism is almost normal. It's as if the chain of pathogenic events is broken after amyloid. The woman is homozygous for the ApoE Christchurch mutation, which seemed to block secondary tau pathology. This protective effect is similar to, but greater than, that of homozygosity for ApoE2. Project aims: We wish to confirm whether homozygosity for the ApoE Christchurch mutation in persons homozygous for ApoE3 can protect against Alzheimer's disease. If so, our results may lead to new treatments. Project duration: one year Public health impact: Our study may hasten new treatments for Alzheimer'd disease14 Publications
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