Development and Validation of Models for Alzheimers Disease-Related Dementias (ADRD) (R61/R33 - Clinical Trial Not Allowed) | PAR 23 154

Opportunity Information: Apply for PAR 23 154

The National Institutes of Health (NIH) funding opportunity PAR-23-154, titled "Development and Validation of Models for Alzheimers Disease-Related Dementias (ADRD) (R61/R33 - Clinical Trial Not Allowed)," is a discretionary grant program designed to push the field toward more clinically relevant experimental models of Alzheimers disease and related dementias, including dementias that develop after traumatic brain injury (post-TBI dementias). The central aim is to support both the creation of new models and the rigorous validation of those models so they better mirror what actually happens in people, rather than producing findings that only apply in narrow laboratory settings.

This opportunity focuses on model systems that can be used to study disease mechanisms and, importantly, to support therapy development by improving confidence that preclinical results will translate into humans. NIH is open to a wide range of model types, including small animal models (such as rodents), larger animal models, ex vivo models (for example, organotypic slice cultures or explanted tissues), human induced pluripotent stem cell (iPSC)-based systems, and other in vitro approaches. The emphasis is not on using a single preferred platform, but on whether the model can credibly represent human AD/ADRD biology, progression, and clinical features. Because the announcement explicitly states "Clinical Trial Not Allowed," the work should be preclinical or mechanistic rather than interventional studies in human participants that meet the NIH definition of a clinical trial.

A major feature of this FOA is the expectation of thorough validation. Applicants are encouraged to build a convincing case that a proposed model is not just novel, but meaningfully aligned with human disease. Validation may include internal validation (showing the model is stable, reproducible, and behaves consistently), face validation (the model resembles human disease features such as pathology, cognitive impairment, or biomarker patterns), construct validation (the biology and causal mechanisms match what is believed to drive disease in humans), and predictive validation to the extent possible (the model responds to interventions in ways that are consistent with human outcomes, or at least aligns with known therapeutic successes and failures where relevant). The FOA highlights multiple ways to do this, including interrogating underlying mechanisms and pathways, using functional imaging, assessing behavior, and collecting cognitive or other functional readouts that connect more directly to clinical symptoms. Independent replication is also encouraged, reflecting NIHs interest in models that stand up across labs and are not overly dependent on a single set of hands or a single experimental environment.

NIH also signals strong interest in models that reflect the complexity of real-world disease, not just isolated pieces of pathology. Novel models of complex pathology, mixed etiologies, or comorbid conditions are encouraged. In practical terms, this could mean models that incorporate multiple risk factors and interacting variables such as genetics, age, environment, lifestyle exposures, vascular contributions, metabolic factors, inflammation, or prior brain injury. The goal is to better capture the kinds of multifactor interactions seen in patients, where AD/ADRD often develops over time and alongside other health conditions. New models are expected to be innovative and to fill a clear gap in the current landscape of AD/ADRD models, rather than being minor variations of existing approaches.

The activity uses an R61/R33 phased innovation mechanism. In general, this type of structure is intended to support an initial, milestone-driven development stage (R61) followed by a second stage focused on expanded validation and/or further development (R33), with progression tied to successful completion of predefined objectives. The funding instrument is a grant under NIH, and the activity category is health-related research. The opportunity lists CFDA numbers 93.853 and 93.866, reflecting the NIH programs under which the funding is administered. The posted award ceiling is $360,000, and the original closing date shown in the source information is 2023-10-20.

Eligibility is broad and includes many domestic U.S. organization types: 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; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status; for-profit organizations (other than small businesses); and small businesses. The FOA also highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISIs, Hispanic-serving institutions, historically Black colleges and universities (HBCUs), tribally controlled colleges and universities (TCCUs), faith-based or community-based organizations, regional organizations, eligible federal agencies, and U.S. territories or possessions. Foreign institutions (non-U.S. entities) are stated as not eligible to apply as applicant organizations, but non-domestic components of U.S. organizations are eligible, and foreign components are allowed as defined by the NIH Grants Policy Statement, meaning a U.S. applicant can include certain project elements performed abroad when justified and compliant with NIH policy.

Overall, the grant is aimed at strengthening the foundation of AD/ADRD research by producing models that are both more human-relevant and more rigorously tested. NIH is clearly trying to address a persistent bottleneck in dementia research: having experimental systems that can reliably predict human biology and therapeutic response. Applicants that can show a genuine unmet need in current models, propose a thoughtful plan to demonstrate internal consistency and clinical relevance, and incorporate the complexity of patient risk profiles and comorbidities are aligned with the core intent of this opportunity.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Development and Validation of Models for Alzheimers Disease-Related Dementias (ADRD) (R61/R33 - 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 2023-04-11.
• Applicants must submit their applications by 2023-10-20. (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 $360,000.00 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 23 154

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