The Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment (Funding Opportunity Number PAR-25-224) is issued by the National Institutes of Health through the National Institute on Aging (NIA). This funding opportunity seeks to advance a comprehensive, cross-disciplinary understanding of how sex differences impact molecular mechanisms underlying Alzheimer’s disease (AD), AD-related dementias (ADRD), and responsiveness to interventions. The goal is to improve the understanding of sex-related molecular trajectories in brain aging and neurodegeneration and develop insights into precision medicine for AD treatment and prevention.

This initiative focuses on integrating experimental, computational, basic, and clinical research to study the effects of sex differences on AD risk and progression. Applications should explore topics such as molecular mechanisms of brain aging, sex-specific vulnerabilities to metabolic, inflammatory, and vascular risk factors, hormonal transitions’ effects on AD pathology, and responsiveness to pharmacologic and non-pharmacologic interventions. Studies may utilize human biosamples and datasets, multi-omics data, imaging, clinical data, and other multimodal resources to investigate these critical areas. Proposals relying solely on cell-based or animal models, or focused on evaluating intervention efficacy, will not be considered responsive to this opportunity.

Eligible applicants include higher education institutions, nonprofits, for-profits, small businesses, local and state governments, tribal organizations, and foreign entities. Collaborative, team-science approaches are encouraged, especially those incorporating diverse expertise in neuroscience, physiology, computational biology, and translational research. Projects may include mechanistic clinical trials, which aim to understand the biological or behavioral mechanisms behind AD risk, resilience, or treatment response. Applications must demonstrate adherence to rigorous scientific standards, open science practices, and FAIR (Findable, Accessible, Interoperable, and Reusable) principles for data and resource sharing. Data and tools generated must be deposited into the NIA-supported AD Knowledge Portal or other designated repositories for broad accessibility.

There is no budget cap for proposals; budgets should reflect the project’s actual needs. The maximum project period is five years. All applications are due by 5:00 PM local time on February 21, 2025. Applicants requesting $500,000 or more in direct costs for any year must contact NIA scientific staff at least six weeks before submission. Letters of intent are due 30 days prior to the application deadline. Reviews will focus on the importance of the research, the rigor and feasibility of the proposed approach, and the expertise and resources available to carry out the project.

Applications will be evaluated for scientific merit through NIH’s peer review process and for alignment with NIA’s priorities. Award decisions will consider the scientific merit, program relevance, adherence to open-science principles, and available funding. Successful projects are expected to generate high-quality, reproducible findings that inform sex-specific molecular determinants of AD and ADRD risk and treatment outcomes. Recipients must deposit all generated data, analytical methods, and resources within designated repositories and ensure that findings are broadly accessible without embargo.

For inquiries, applicants are encouraged to contact NIA program staff early in the pre-submission process. Specific contacts include Dr. Shreaya Chakroborty for scientific/research questions at shreaya.chakroborty@nih.gov and Dr. Ramesh Vemuri for peer review questions at ramesh.vemuri@nih.gov. Financial and grants management inquiries should be directed to Jillian Morris at morrisjil@mail.nih.gov.