Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD and other ADRDs (R01 - Clinical Trial Not Allowed) | PAR 24 148

Opportunity Information: Apply for PAR 24 148

The NIH funding opportunity PAR 24-148 is an R01 grant focused on TDP-43 proteinopathies, with an emphasis on building stronger, more causal mechanistic links between TDP-43 pathology and the clinical and biological outcomes seen in aging and neurodegenerative disease. The scientific goal is not simply to document that TDP-43 aggregates are present, but to explain how and why TDP-43 pathology develops, what it does to cells and circuits, and which mechanisms are shared versus distinct across related conditions. The FOA explicitly includes LATE (limbic-predominant age-related TDP-43 encephalopathy), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and other Alzheimer s disease-related dementias (ADRDs), and it encourages work that can clarify how TDP-43 contributes to different phenotypes in different disease contexts.

A central priority is mechanistic insight and causality. Applications are expected to move beyond correlation by testing mechanisms that connect TDP-43 pathology to downstream effects such as neuronal dysfunction, neurodegeneration, network disruption, and measurable cognitive or behavioral changes. Projects may approach this through molecular and cellular studies, structural biology, genetics, neuropathology, or multi-omics, as long as the work is designed to reveal cause-and-effect relationships or clearly defined mechanistic pathways. The FOA also highlights interest in how TDP-43 interacts with other co-pathologies rather than acting in isolation, including mechanistic interactions with factors like TMEM106B, which has been linked to risk and disease modification in TDP-43 related disorders.

Another major theme is comparison across TDP-43 proteinopathies to identify what is shared and what is unique. The announcement specifically calls for comparative studies across conditions such as LATE (including LATE with or without Alzheimer s disease neuropathologic change, often abbreviated AD-NC), FTD, and ALS. The comparisons can be carried out across many levels of analysis, including mechanistic, molecular, structural, cellular, genetic, -omic, anatomical, and neuropathological dimensions. In practice, this means the FOA is well-suited to proposals that systematically map and contrast TDP-43 strain-like properties, cell-type vulnerability, regional spread patterns, transcriptomic or proteomic signatures, genetic modifiers, or interactions with other hallmark pathologies. The underlying expectation is that these comparisons will help explain why TDP-43 pathology presents differently across syndromes and why similar pathology can produce different clinical outcomes depending on context.

The activity mechanism is an R01, and the FOA is labeled Clinical Trial Not Allowed, meaning the proposed research cannot include a clinical trial as defined by NIH. The work can still be highly translational and may incorporate human data, biospecimens, postmortem tissue, imaging, or observational cohorts, but it must remain within the boundaries of non-trial research. The administering agency is the National Institutes of Health, and the opportunity falls under health-related CFDA numbers 93.853 and 93.866. The listed award ceiling is $500,000, indicating the budget cap presented in the source information for this announcement.

Eligibility is broad and includes many U.S.-based organizational types: state, county, city, and special district governments; public and state-controlled and private institutions of higher education; independent school districts; Native American tribal governments (federally recognized); public housing authorities and Indian housing authorities; nonprofit organizations with or without 501(c)(3) status; for-profit organizations other than small businesses; and small businesses, among others. The FOA also explicitly calls out additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), as well as faith-based or community-based organizations and eligible federal agencies. A key restriction is that non-domestic (non-U.S.) entities are not eligible to apply, and non-domestic components of U.S. organizations are not eligible. However, foreign components are allowed when they meet the NIH definition in the NIH Grants Policy Statement, which can enable discrete parts of the work to be carried out internationally under a U.S. applicant institution.

Key dates provided in the source include a creation date of 2024-02-06 and an original closing date of 2024-10-04. Overall, the opportunity is aimed at advancing a more precise, mechanism-driven understanding of TDP-43 proteinopathies, clarifying how TDP-43 contributes to disease phenotypes, and disentangling how co-pathologies and genetic or molecular modifiers shape progression and clinical expression across LATE, FTD, ALS, and related ADRDs.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD and other ADRDs (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 2024-02-06.
• Applicants must submit their applications by 2024-10-04. (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 24 148

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