Lipids in Brain Aging and Alzheimer's Disease (AD) and its Related Dementias (ADRD) (R01 Clinical Trial Not Allowed) | RFA AG 23 009

Opportunity Information: Apply for RFA AG 23 009

The National Institutes of Health (NIH) released this Funding Opportunity Announcement, RFA-AG-23-009, titled "Lipids in Brain Aging and Alzheimer's Disease (AD) and its Related Dementias (ADRD) (R01 Clinical Trial Not Allowed)." It is a discretionary grant opportunity in the health area (CFDA 93.866) that uses the NIH R01 research project grant mechanism to fund studies that deepen what is known about how lipids shape brain aging and the development or progression of Alzheimer's disease and related dementias. A central theme of the announcement is that lipid biology is increasingly recognized as a major driver of neurodegeneration risk and protection, but key gaps remain in how lipid pathways operate in the aging brain and how they connect to AD/ADRD mechanisms. The FOA is positioned to support projects that are mechanistic, hypothesis-driven, and aimed at generating clear insights into lipid-related processes that could eventually inform prevention, diagnosis, or therapy, while explicitly stating that clinical trials are not allowed under this announcement.

The scientific focus is organized around several priority areas where the NIH is seeking stronger evidence and clearer models. One area is the role of lipid droplets in the brain during aging and AD/ADRD. The FOA highlights that lipid droplets can accumulate in neural and glial cells, but it is still unresolved whether this build-up is harmful, beneficial, or context-dependent. Proposed research could clarify when lipid droplet formation reflects metabolic stress and dysfunction versus when it serves as a protective buffer for toxic lipids, oxidative damage, or inflammation, and how these dynamics intersect with known AD/ADRD pathologies. Another priority area is the interaction between peripheral lipid biology and lipids in the aging brain. This includes examining how systemic metabolism, circulating lipids, liver or adipose signaling, vascular factors, or immune components influence brain lipid composition and function over time. The FOA also points to the possibility that peripheral lipid measures or lipid-related signals could become targets for future biomarkers, meaning the research may help identify measurable indicators that correlate with brain aging trajectories or dementia risk, even if the projects themselves are not clinical trials.

A third emphasized topic is APOE and lipid-mediated signaling. APOE is one of the strongest genetic risk factors for late-onset Alzheimer's disease, and the FOA calls for research that disentangles how APOE isoforms alter lipid handling, lipid transport, receptor signaling, inflammation, synaptic function, and cellular resilience in ways that influence brain aging and AD/ADRD progression. This can include work on downstream lipid signaling pathways, cell-type specific effects (for example, astrocytes, microglia, oligodendrocytes, neurons), and how APOE-related lipid biology interacts with other disease drivers. The fourth major area involves myelin lipids and their signaling. Because myelin is lipid-rich and essential for efficient neural communication, changes in myelin lipid composition, turnover, repair, and signaling could contribute to age-related cognitive decline and dementia vulnerability. The FOA encourages studies that examine how myelin lipid integrity is maintained or lost with age, how demyelination or remyelination relates to neuroinflammation and neurodegeneration, and what lipid pathways in oligodendrocytes or myelin-associated cells may be leveraged to promote resilience.

From an administrative and eligibility standpoint, this opportunity is open to a broad range of applicant organizations. Eligible applicants include various levels of government (state, county, city or township, and special district governments), independent school districts, public housing authorities/Indian housing authorities, public and state-controlled institutions of higher education, private institutions of higher education, and federally recognized Native American tribal governments. It also includes Native American tribal organizations that are not federally recognized tribal governments, nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those categories), for-profit organizations other than small businesses, and small businesses, as well as other eligible entities. The FOA also explicitly calls out additional eligible groups 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), eligible federal agencies, faith-based or community-based organizations, U.S. territories or possessions, regional organizations, and non-U.S. entities (foreign organizations). This wide eligibility suggests NIH interest in attracting multidisciplinary teams and diverse institutional perspectives, including those with specialized community connections, unique populations, or distinctive scientific capabilities.

The opportunity lists an award ceiling of $500,000, indicating an upper bound on supported costs as presented in the source summary. It was created on 2021-12-28, with an original closing date of 2022-06-14. Overall, the announcement is aimed at accelerating foundational and translationally relevant understanding of lipid-related mechanisms in brain aging and AD/ADRD, with particular attention to lipid droplets, brain-periphery lipid interactions and biomarker potential, APOE-driven lipid signaling, and myelin lipid biology, all within the non-clinical-trial R01 framework.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Lipids in Brain Aging and Alzheimer's Disease (AD) and its Related Dementias (ADRD) (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 2021-12-28.
• Applicants must submit their applications by 2022-06-14. (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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