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 23 082

Opportunity Information: Apply for PAR 23 082

The National Institutes of Health (NIH) is offering a discretionary funding opportunity under a cooperative agreement mechanism (U01), titled "Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (Clinical Trial Optional)." The focus is Alzheimer disease (AD) and AD-related dementias (ADRD), specifically the ways sex differences shape how the brain ages, how disease risk develops, what clinical and biological phenotypes emerge, and how people respond to both drug-based and non-drug interventions. Because the U01 is a cooperative agreement, awardees should expect an active partnership with NIH program staff compared with a standard research grant, often involving coordination, shared milestones, and programmatic involvement to help drive the overall goals of the initiative.

The central scientific aim is to build integrative, multi-level research programs that connect basic biology with translational and, where appropriate, clinical research. The FOA emphasizes combining experimental and analytical approaches to create a more complete picture of how sex differences influence AD/ADRD trajectories from early brain aging through disease onset and progression. Applicants are encouraged to address heterogeneity: rather than treating AD/ADRD as a single uniform condition, the initiative pushes teams to explain why risk and treatment responsiveness can look different across individuals, and how sex-related biology contributes to those differences.

A key theme is interaction among genes, environment, and host factors, with particular attention to hormonal status, including both gonadal hormones and hormones produced within the brain. The FOA is looking for research that can explain how these influences interact across multiple levels of biological complexity. That includes work at the level of cells and molecular pathways, through tissues and organ systems (such as brain-immune or brain-vascular interfaces), and extending to human populations. In practice, this points to projects that can link mechanistic findings (for example, sex-linked differences in molecular signaling, immune responses, synaptic resilience, or protein clearance pathways) to measurable phenotypes in people, such as biomarker profiles, cognitive trajectories, or differential response to prevention and therapy.

The opportunity also stresses individualized prevention and responsiveness to interventions, meaning projects should ideally inform why prevention strategies or treatments might work better in some groups than others, and how sex differences contribute to that pattern. Importantly, the announcement is labeled "Clinical Trial Optional," so a project may include a clinical trial if it is scientifically justified, but it does not have to. This leaves room for a wide range of study designs, from preclinical mechanistic studies to human observational cohorts, biomarker-driven translational studies, and intervention research, as long as they are integrated and aligned with the overarching goal of understanding sex differences in AD/ADRD risk and treatment response.

Eligibility is broad and includes many types of U.S. organizations and governments: state, county, city, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those categories as specified); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly highlights additional eligible applicant categories such as 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), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations). This broad eligibility signals an intent to encourage diverse institutions and communities to participate, including groups that may bring unique population data, community partnerships, or specialized scientific capabilities relevant to sex differences and AD/ADRD.

From the provided source details, the Funding Opportunity Number is PAR 23 082, the CFDA number listed is 93.866, and the opportunity is categorized under health-related research. The original closing date is February 21, 2025, and the record creation date is January 10, 2023. The notice does not provide an award ceiling or expected number of awards in the excerpt you shared, so applicants would need to consult the full FOA text and any linked NIH institute-specific budget guidance for details on allowable budgets, project periods, and program expectations. Overall, the opportunity is geared toward coordinated, integrative research that can move the field beyond simple comparisons between males and females and toward a deeper, mechanistic and clinically meaningful understanding of how sex-related biology shapes AD/ADRD risk and treatment outcomes.

• 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 2023-01-10.
• Applicants must submit their applications by 2025-02-21. (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 23 082

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