Disease Mechanisms: APOE physiology (Milestone 2.E)
Achieved
Timeline Start - End
2016 - 2020Research Implementation Area
Research on Disease MechanismsCreate cross-disciplinary research programs aimed at understanding the integrative physiology of APOE and its pharmacogenetic effects on various pharmacological and non-pharmacological interventions.
Success Criteria
- Launch at least 10 cross-disciplinary projects aimed at developing a deeper understanding of the protective and risk factor properties of APOE and its pharmacogenetic effects on various pharmacological and non-pharmacological interventions. Of these, at least three projects should be focused on understanding the mechanisms of risk reduction by APOE2.
Summary of Key Accomplishments
Apolipoprotein E (ApoE) is a lipid transporter that plays an important role in cardiovascular disease, exceptional longevity, and AD. It also influences the response to various therapeutic interventions. Different forms of ApoE are associated with differences in risk for AD: ApoE4 is the strongest genetic risk factor for late onset AD, while ApoE2 is associated with reduced risk of AD. NIA supports a large portfolio of research grants focused on understanding the mechanisms by which the various forms of ApoE influence the onset and progression of AD and how they interact with sex and aging leading to different disease outcomes. Through two targeted funding initiatives, NIA has supported 27 research projects focused on understanding the mechanisms by which ApoE2 confers neuroprotection and reduces risk of AD. For example, a study of three large groups of research study participants found that ApoE2 resilience to AD may be affected by the number and type of lipids in the blood. Findings from this study and others may inform new therapeutic opportunities. Information about a person’s ApoE status is already being used to help develop less-invasive tests for amyloid. A recently developed blood test (PrecivityAD), supported in part by NIA small business grants, checks for the presence and type of ApoE, which is used to help increase the accuracy of the test.
The key accomplishments summary is current as of March 2022.
Accomplishments/Implementation Activities
Funding Initiatives
- PAR-16-370: Phenotypic and Functional Characterization of ApoE2 to Inform Translation Strategies for Aging-Related Conditions (R01)
- PAR-16-371: Phenotypic and Functional Characterization of ApoE2 to Inform Translation Strategies for Aging-Related Conditions (R21)
- RFA-AG-17-056: Understanding the Effects of ApoE2 on the Interaction between Aging and Alzheimer’s Disease (R01)
- RFA-AG-18-022: Understanding the Effects of ApoE2 on the Interaction between Aging and Alzheimer’s Disease (R01)
- PAR-15-358: Capturing Complexity in the Molecular and Cellular Mechanisms Involved in the Etiology of Alzheimer’s Disease (R01)
- PAR-19-070: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
- PAR-19-071: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
- NOT-AG-21-041: Capturing Complexity in the Molecular and Cellular Mechanisms Involved in the Etiology of Alzheimer's Disease
Research Programs and Resources
- Phenotypic and Functional Characterization of ApoE2 to Inform Translation Strategies for Aging-Related Conditions (R01)
- Phenotypic and Functional Characterization of ApoE2 to Inform Translation Strategies for Aging-Related Conditions (R21)
- Understanding the Effects of ApoE2 on the Interaction between Aging and Alzheimer’s Disease (R01)
- Capturing Complexity in the Molecular and Cellular Mechanisms Involved in the Etiology of Alzheimer’s Disease (R01)
- Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
- Identifying Protective Genetic Variants for APOE4
Research Highlights
Relevant Recommendations
- 2015 AD Summit Recommendations: 3H
- Aging disrupts the normal daily fluctuations of immune cell activity