Understanding the Effects of ApoE2 on the Interaction between Aging and Alzheimers Disease (R01 - Clinical Trial Not Allowed) | RFA AG 18 022

Opportunity Information: Apply for RFA AG 18 022

The National Institutes of Health (NIH) funding opportunity titled "Understanding the Effects of ApoE2 on the Interaction between Aging and Alzheimers Disease (R01 - Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-AG-18-022) supports research aimed at clarifying how the APOE2 variant influences healthy aging and modifies risk related to Alzheimers disease (AD). The central idea behind the announcement is that ApoE2 is widely viewed as a protective genetic variant in the context of AD, but the field still needs a clearer, mechanistic understanding of what ApoE2 is doing in the brain and across the body as people age, and how those actions might reduce vulnerability to cognitive decline and AD-related pathology. The NIH is seeking studies that can move beyond simple associations and produce deeper biological insight into why ApoE2 protection occurs and how it might be leveraged for prevention, diagnosis, or treatment development.

The scope of work emphasized in the announcement includes descriptive, basic, and translational research on APOE2. Applications are expected to focus on the ApoE2-Aging-AD relationship, meaning the ways ApoE2 affects aging processes and how those altered aging trajectories intersect with AD initiation or progression. A key theme is mechanism: projects should aim to explain functional effects of ApoE2 rather than only documenting outcomes. This can include investigating how ApoE2 impacts cellular and molecular pathways relevant to brain aging (such as lipid transport and metabolism, inflammation, synaptic function, vascular integrity, protein aggregation and clearance, or glial biology), as well as understanding how ApoE2 may shape resilience to age-related stresses that contribute to neurodegeneration.

Another major priority is the potential interaction or crosstalk between tissues during aging and AD. The announcement explicitly invites work that considers not only the brain, but also other organs and systems that may influence brain health during aging. This reflects growing recognition that AD risk and cognitive aging are not purely brain-isolated problems, and that systemic factors (for example, immune signaling, metabolic regulation, cardiovascular and cerebrovascular function, liver and lipid biology, or peripheral inflammation) can meaningfully alter brain aging and AD-related processes. Competitive projects under this FOA would likely connect ApoE2-driven biology in the brain to changes in other tissues, or identify multi-organ pathways through which ApoE2 confers protection.

The expected outcomes of funded studies include generating new mechanistic insights that may point to practical downstream applications. The NIH highlights the value of identifying prognostic and diagnostic markers, which could include biomarkers indicating protective ApoE2-related pathways, signatures of slowed or altered aging, or indicators of reduced AD vulnerability. The FOA also points to therapeutic targets, suggesting that understanding ApoE2 biology could reveal druggable pathways or strategies that mimic ApoE2-like protective effects even in people who do not carry the APOE2 allele. Although the FOA is not for clinical trials, it is framed as foundational work that could eventually enable translational research opportunities, including approaches intended to prevent or delay AD onset and potentially protect against multiple age-related conditions, not just dementia.

This opportunity uses the NIH R01 grant mechanism and is labeled "Clinical Trial Not Allowed," meaning proposed studies must not include clinical trial components as defined by NIH policy. It falls under a health-focused activity category and is associated with CFDA number 93.866. The posted award ceiling is $500,000, and the original closing date listed is March 28, 2018, indicating it was time-limited and anchored to that submission window.

Eligibility is broad and includes many types of applicants, such as state, county, and local governments; public and private institutions of higher education; nonprofit organizations (with or without 501(c)(3) status); for-profit organizations (other than small businesses); small businesses; independent school districts; special district governments; and public housing authorities/Indian housing authorities. It also includes Native American tribal governments (federally recognized) and tribal organizations (other than federally recognized governments). The FOA explicitly encourages participation from a wide range of institutions and organizations, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible federal agencies, faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and even non-U.S. (foreign) entities.

In practical terms, the FOA is designed to push the field toward a more complete biological explanation of ApoE2-mediated protection across aging, with an emphasis on rigorous mechanistic work that can illuminate where, when, and how ApoE2 changes aging biology in ways that reduce AD risk. The long-range rationale is that once those protective mechanisms are clearly mapped, they can inform better biomarkers, earlier risk stratification, and new therapeutic concepts aimed at extending cognitive healthspan and reducing the burden of AD and related age-associated cognitive disorders.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Understanding the Effects of ApoE2 on the Interaction between Aging and Alzheimers Disease (R01 - Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.866.
• This funding opportunity was created on 2017-12-21.
• Applicants must submit their applications by 2018-03-28. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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