Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (U01 Clinical Trial Optional) | PAR 22 228

Opportunity Information: Apply for PAR 22 228

This grant opportunity, PAR 22-228, is a National Institutes of Health (NIH) Funding Opportunity Announcement that supports cooperative agreement projects (U01 mechanism) focused on Alzheimer disease (AD) and Alzheimer disease-related dementias (ADRD). The program is designed to push beyond broad, averaged findings by building a clearer, more biologically grounded picture of how sex differences shape brain aging, AD/ADRD risk, and how people respond to prevention strategies and treatments. The “Clinical Trial Optional” designation means applicants may propose studies that include clinical trials, but they are not required to do so; projects can be basic, translational, clinical, or integrative across these areas as long as they align with the core goals.

The scientific emphasis is on integrative experimental and analytical approaches that connect multiple layers of biology and evidence. NIH is looking for research programs that can explain how sex differences influence disease trajectories and heterogeneity, including why different individuals develop different AD/ADRD phenotypes, progress at different rates, or respond differently to interventions. Rather than treating sex as a simple demographic variable, the FOA highlights sex-related biology as a central driver to be studied directly, including interactions among genes, environment, and host factors. A specific host factor called out in the announcement is hormonal status, including both gonadal hormones and hormones produced within the brain, reflecting interest in how endocrine and neuroendocrine influences may alter molecular pathways relevant to neurodegeneration, resilience, and treatment response.

A key expectation is that funded projects will examine these interactions at multiple levels of biological complexity. The FOA explicitly mentions work spanning cells, tissues, organs or organ systems, and populations. In practical terms, that could include mechanistic laboratory studies (for example, cell-based or animal model work examining sex-linked molecular pathways), translational efforts that bridge model systems to human biology (for example, biomarker development or validation), and clinical or population-based analyses (for example, cohort studies or carefully designed intervention studies that can evaluate sex-specific risk profiles or treatment effects). The end goal is a more comprehensive framework for individualized prevention and therapy in AD/ADRD that takes sex differences seriously as part of precision medicine, rather than treating them as a secondary analysis.

From a funding and administrative standpoint, this is a discretionary health research opportunity under CFDA 93.866 and uses the cooperative agreement structure, which typically means NIH program staff have a more active role than they would under a standard research project grant. That structure is often used when a program benefits from coordination, shared expectations, or stewardship to ensure the research stays aligned with program goals and generates broadly useful outputs. The source information provided does not list an award ceiling or expected number of awards, indicating those details may vary or be defined in the full FOA and related NIH budget guidance.

Eligibility is broad and includes many types of organizations that can carry out high-quality biomedical research. Eligible applicants include state, county, city, and special district governments; public and state-controlled institutions of higher education; private institutions of higher education; independent school districts; federally recognized Native American tribal governments and other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses) as well as small businesses; and other entities. The FOA also explicitly highlights additional eligible applicants such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), faith-based or community-based organizations, regional organizations, eligible federal agencies, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). This wide eligibility signals an interest in drawing on diverse institutional strengths, multidisciplinary teams, and potentially broader population perspectives.

The opportunity was created on 2022-08-16 and listed an original closing date of 2023-01-10 in the provided data. Overall, the program is best understood as NIH support for rigorous, multi-level research that can clarify how sex-linked biology and hormone-related factors intersect with genetics and environment to shape AD/ADRD risk and clinical outcomes, with the practical aim of enabling more tailored prevention and treatment strategies for different individuals.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (U01 Clinical Trial Optional)" 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 2022-08-16.
• Applicants must submit their applications by 2023-01-10. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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.

Apply for PAR 22 228

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: