Neuronal Vulnerability to Proteinopathies in Alzheimers Disease and Alzheimers Disease-Related Dementias (R01 Clinical Trial Not Allowed) | RFA AG 23 028

Opportunity Information: Apply for RFA AG 23 028

The grant opportunity titled "Neuronal Vulnerability to Proteinopathies in Alzheimers Disease and Alzheimers Disease-Related Dementias (R01 Clinical Trial Not Allowed)" (Funding Opportunity Number RFA-AG-23-028) is a discretionary research grant offered by the National Institutes of Health (NIH) under the health research activity category (CFDA 93.866). It uses the R01 mechanism, meaning it is intended to support substantial, hypothesis-driven projects that can define a clear scientific problem and deliver meaningful advances over a multi-year period. The "Clinical Trial Not Allowed" designation indicates the work should be basic, translational, or mechanistic in nature rather than testing an intervention in humans using a clinical trial design.

The scientific focus of this Funding Opportunity Announcement (FOA) is on understanding which specific neuronal and glial cell populations are most vulnerable to the damaging protein pathologies seen in Alzheimers disease (AD) and Alzheimers disease-related dementias (ADRD). In practical terms, the FOA is looking for projects that can identify, define, and characterize the brain cell types and subtypes that are preferentially affected by disease-associated protein accumulation and misfolding (often referred to broadly as "proteinopathies"). By emphasizing both neurons and glia, the announcement underscores that AD/ADRD is not only a neuron-centric disorder; changes in microglia, astrocytes, oligodendrocytes, and other support cells can shape inflammation, synaptic health, myelination, metabolism, and clearance of pathological proteins, all of which can influence why certain circuits and regions deteriorate earlier or more severely than others.

A key theme implied by the FOA is cell-type-specific vulnerability: why some populations resist pathology while others succumb. Projects responsive to this goal typically aim to map vulnerability across brain regions, developmental lineages, molecular states, or connectivity patterns, then link those patterns to the presence and progression of AD/ADRD-associated protein abnormalities. The overall intent is to generate clearer biological explanations for selective degeneration and to provide a stronger foundation for future therapeutic strategies that target the right cells, pathways, and disease stages. While the FOA text provided here is brief, the objective naturally aligns with modern approaches such as high-resolution cell profiling, spatial or circuit-level mapping, and mechanistic studies that connect proteinopathy burden with cellular stress responses, immune signaling, synaptic dysfunction, or failures in proteostasis and clearance pathways.

Eligibility is broad and includes a wide range of U.S. and non-U.S. organizations. Standard eligible applicants listed include state, county, city or township 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; tribal organizations that are not federally recognized; public housing authorities/Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education when relevant); for-profit organizations other than small businesses; small businesses; and other eligible entities. The FOA also explicitly highlights additional eligible applicant types that NIH wants to encourage, including Alaska Native and Native Hawaiian Serving Institutions; Asian American Native American Pacific Islander Serving Institutions (AANAPISI); faith-based or community-based organizations; Hispanic-serving Institutions; Historically Black Colleges and Universities (HBCUs); Indian/Native American Tribal Governments (other than federally recognized); Tribally Controlled Colleges and Universities (TCCUs); regional organizations; U.S. territories or possessions; eligible federal agencies; and non-domestic (non-U.S.) entities (foreign organizations). This breadth signals an interest in widening participation and leveraging diverse scientific environments and populations, including organizations that may bring unique strengths in neuroscience, neuropathology, computational biology, or community-engaged research infrastructure (even though the award itself is not for clinical trials).

The opportunity was created on April 19, 2022, with an original closing date of July 15, 2022. The award ceiling and expected number of awards are not specified in the source information provided, which often means applicants need to consult the full FOA and NIH funding policies to understand typical budget expectations, project period norms, and institute-specific constraints for R01s. Overall, this FOA is aimed at advancing a more precise and cell-resolved understanding of how AD/ADRD proteinopathies impact the brain, with the longer-term payoff of enabling better-targeted interventions, biomarkers, and disease models grounded in the biology of vulnerable neuronal and glial populations.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Neuronal Vulnerability to Proteinopathies in Alzheimers Disease and Alzheimers Disease-Related Dementias (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 2022-04-19.
• Applicants must submit their applications by 2022-07-15. (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 RFA AG 23 028

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