Longitudinal Single Cell Characterization of ADRD Postmortem Tissue (R01 Clinical Trial Not Allowed) | PAR 22 029

Opportunity Information: Apply for PAR 22 029

The National Institutes of Health (NIH) funding opportunity PAR 22 029, titled "Longitudinal Single Cell Characterization of ADRD Postmortem Tissue (R01 Clinical Trial Not Allowed)," supports research projects that use modern single-cell and single-nucleus technologies to better understand Alzheimer’s disease and related dementias (ADRD) by studying human postmortem brain tissue. The central scientific focus is on the hippocampus, a brain region strongly tied to memory and early disease changes, and specifically on individuals who were experiencing mild cognitive impairment (MCI), often considered an earlier symptomatic stage on the pathway toward dementia. The overall intent is to map, with high resolution, how different brain cell populations shift during this stage, and to make those findings interoperable with major national reference resources.

The FOA is built around three connected goals. First, applicants are expected to generate single-cell or single-nucleus omics profiles from MCI autopsy brains, emphasizing transcriptomic and epigenetic measurements. In practical terms, this means characterizing gene expression programs and regulatory states within key cell classes in the hippocampus, including neuronal cells, glial cells (such as astrocytes, microglia, and oligodendrocytes), and vascular-associated cells. The FOA explicitly calls for analyzing changes in cell identity, cell number, and/or morphology, so projects are expected not only to catalog cell types and states, but also to assess how those populations expand, contract, or change in ways that may reflect early disease mechanisms. This kind of work is meant to clarify which cell types are affected first, what molecular pathways are altered in MCI, and how those alterations might relate to later neurodegeneration.

Second, the FOA asks applicants to propose a data coordination center function that will bring together single-cell or single-nucleus datasets produced across a consortium using different tissue sources and a range of well-documented tissue processing and preparation methods. A major challenge in postmortem single-cell work is that results can be highly sensitive to how tissue is handled, dissociated, nuclei are isolated, frozen, preserved, or otherwise prepared. By collecting and comparing datasets generated under diverse but well-described conditions, the coordination effort is intended to identify which technical variables most strongly influence data quality and biological interpretation. The outcome NIH is pushing for here is a clearer understanding of the critical factors needed for robust, accurate, and reproducible single-cell(-nuc) omics analysis in human ADRD tissue, helping the field avoid misleading conclusions that arise from batch effects or preparation artifacts.

Third, the FOA prioritizes harmonization with the BRAIN Initiative’s human cell census efforts. The expectation is that funded projects will align their cell type definitions, annotations, and data structures with the BRAIN Initiative human brain cell type reference and registry, which is largely built from analyses of healthy human brain. By coordinating ADRD-focused single-cell datasets with these healthy reference atlases, investigators can more directly compare disease tissue to normal baselines, use standardized cell type labels, and integrate results across studies. This also makes the data more reusable by the broader research community, since a common cell type registry and shared conventions reduce friction when combining datasets from different labs and consortia.

From an administrative standpoint, this is an NIH discretionary grant opportunity using the R01 mechanism, and it explicitly does not allow clinical trials. The funding activity category is health, and the listed CFDA numbers are 93.853 and 93.866. The opportunity lists an award ceiling of 630,000 (as provided in the source data). The original closing date shown is 2021-10-22, with a creation date of 2021-09-02. While the summary does not provide full budget period details, the R01 mechanism generally supports multi-year research projects, and applicants would be expected to propose a coherent research plan and data sharing/coordination approach consistent with NIH expectations for omics and consortium-style work.

Eligibility is broad and includes many types of U.S. organizations and some non-U.S. entities. Eligible applicants include state, county, and local governments; 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; other tribal organizations; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those categories); for-profit organizations other than small businesses; and small businesses. The FOA also highlights additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), 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, non-domestic (non-U.S.) entities (foreign organizations), Indian/Native American Tribal Governments other than federally recognized entities, and U.S. territories or possessions. This breadth signals NIH’s interest in drawing expertise from a wide range of institutions, including those serving historically underrepresented communities and those with specialized capacity in brain banking, neuropathology, single-cell genomics, and data coordination.

In plain terms, this FOA is trying to push the ADRD field toward a more standardized, high-resolution, and interoperable view of early disease-related cellular changes in the human hippocampus. It funds the generation of single-cell(-nuc) transcriptomic and epigenetic datasets from MCI postmortem tissue, requires a strong plan for coordinating and learning from methodological diversity across sites, and strongly encourages alignment with the BRAIN Initiative’s human cell census so ADRD datasets can be compared to healthy references and plugged into a shared cell type framework.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Longitudinal Single Cell Characterization of ADRD Postmortem Tissue (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): 93.853, 93.866.
• This funding opportunity was created on 2021-09-02.
• Applicants must submit their applications by 2021-10-22. (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 $630,000.00 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.

Apply for PAR 22 029

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