Prodromal Synaptic and Circuit Changes that Contribute to AD/ADRD Onset and Progression (R01 Clinical Trial Not Allowed) | PAR 22 059

Opportunity Information: Apply for PAR 22 059

The NIH funding opportunity PAR-22-059, titled "Prodromal Synaptic and Circuit Changes that Contribute to AD/ADRD Onset and Progression (R01 Clinical Trial Not Allowed)," supports research aimed at pinpointing the earliest brain changes that set the stage for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRD). The central focus is on prodromal, preclinical, or very early-stage shifts in synaptic activity, circuit plasticity, and network function that may drive or accelerate downstream neurodegeneration. In practical terms, the FOA is looking for mechanistic studies that move beyond describing pathology and instead explain how changes in neuronal communication and circuit dynamics contribute to disease onset and progression, ideally in ways that could later inform preventative or early-intervention strategies.

A major theme in the announcement is the need for strong in vivo relevance. NIH is explicitly encouraging model development and model use that can capture circuit-level and network-level phenomena in living systems, since synaptic and circuit dysfunction is often context-dependent and may not fully emerge in simplified preparations. Applicants are encouraged to leverage technologies advanced through NIH BRAIN programs, which commonly include modern tools for measuring and manipulating neural activity at high spatial and temporal resolution (for example, approaches for monitoring circuit activity, mapping connectivity, or perturbing defined cell types to test causality). While cell-based and organoid-based systems can be useful for discovery, the FOA draws a clear boundary: proposals that rely entirely on cell culture or organoids are considered out of scope. Those platforms can be part of a broader strategy, but there needs to be an animal-based or otherwise in vivo component that validates whether insights from reductionist systems actually hold up in intact neural circuits.

The award mechanism is an NIH R01 research project grant, and clinical trials are not allowed under this solicitation, meaning the supported work should be preclinical or basic/translational in nature rather than testing interventions in human participants as a clinical trial. The overall rationale is that a clearer mechanistic understanding of early synaptic and circuit disruptions in AD/ADRD could open more opportunities for future therapeutics by identifying actionable targets or windows of vulnerability before widespread neuronal loss occurs.

From an eligibility perspective, the FOA is broadly open to a wide range of domestic applicants, including state, local, and tribal governments; public and private institutions of higher education; nonprofit organizations with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and other types of eligible entities. The opportunity highlights inclusion of organizations that serve specific communities, such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), and Alaska Native, Native Hawaiian, and Asian American/Native American/Pacific Islander-serving institutions, along with faith-based and community-based organizations and eligible federal agencies. U.S. territories and possessions are also included. Foreign institutions (non-U.S. entities) are not eligible to apply as applicant organizations, but foreign components are allowed under NIH policy, and non-domestic components of U.S. organizations may participate, which provides a pathway for international collaboration without having a foreign institution serve as the primary applicant.

Key administrative details from the source information include the sponsoring agency (National Institutes of Health), the opportunity category (discretionary), and activity area (health), with CFDA numbers listed as 93.853 and 93.866. The posting indicates an award ceiling of $500,000 (as provided in the source data). The FOA was created on 2021-11-03 and lists an original closing date of 2022-02-05, which is important for historical context; anyone considering this topic now would need to check NIH for current or reissued due dates, related active FOAs, or subsequent versions of the announcement.

Overall, this funding opportunity is best suited for teams that can connect early synaptic or circuit-level dysfunction to AD/ADRD mechanisms in living models, ideally using state-of-the-art neural circuit tools, and that can frame their work around causal mechanisms and early disease trajectories rather than late-stage degeneration alone.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Prodromal Synaptic and Circuit Changes that Contribute to AD/ADRD Onset and Progression (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 2021-11-03.
• Applicants must submit their applications by 2022-02-05. (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.

Apply for PAR 22 059

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