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How do different versions of APOE protect against or promote Alzheimer’s over time?
Michael Sasner, Ph.D.
The Jackson Laboratory
Bar Harbor, ME - United States
Background
The apolipoprotein E (APOE) gene provides instructions for making ApoE, a protein thought to help carry fats throughout the body. There are several versions of APOE, each of which has different impacts on Alzheimer’s disease risk. APOE-e4 is associated with increased risk for Alzheimer’s in some populations, APOE-e3 is neutral, APOE-e2 is protective for Alzheimer’s in some populations, and a newly discovered but rare version called the APOE-e3 “Christchurch” has been shown to be protective. While researchers know APOE-e4 increases Alzheimer’s risk in some individuals, it alone is not sufficient to be a cause of Alzheimer’s. Additional factors likely interact with APOE to impact disease risk.
Research Plan
Dr. Michael Sasner and colleagues received additional funding to build upon their 2022 APOE Biology in Alzheimer’s (ABA) grant to expand their work on APOE and Alzheimer’s. Their study involves creating genetically-engineered Alzheimer's-like mice with different APOE variations. Because this mouse model develops multiple hallmark brain changes of Alzheimer’s, including beta-amyloid plaques and tau tangles, it allows the scientific community to study how APOE variations impact such brain changes as the mice age.
Originally, Dr. Sasner and team planned to assess the role of APOE in brain health over time by examining mice at two different points: 4 months of age and 18 months of age. With their supplemental grant, the researchers can now examine mice at three different points: 6, 12, and 18 months of age. This expansion will enable them to better understand the role of APOE in brain health over time. In addition, it will enable the team to assess how APOE affects female mice during and after menopause due to the extended time points. Their analysis will include how APOE may alter female hormone levels during this important transition in life to promote dementia risk.
Impact
Dr. Sasner’s project will shed new light on the role of gene variations of APOE in one’s risk for and resilience to Alzheimer’s. It could also identify novel biology pathways and targets that could offer new therapeutic approaches targeted to people of different ages and sexes. In addition, the project will provide important resources to the broader research community.
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