Role of Peripheral Proteostasis on Brain Aging and Alzheimer's Disease (R01 Clinical Trial Not Allowed) | RFA AG 18 020

Opportunity Information: Apply for RFA AG 18 020

The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), offered this R01 grant opportunity to support research that clarifies how protein homeostasis in peripheral (non-brain) tissues influences brain aging and contributes to Alzheimer s disease (AD). The core idea behind the announcement is that while Alzheimer s research has long emphasized protein aggregation inside the brain, especially amyloid beta and tau, aging affects the body as a whole, and the systems that keep proteins properly folded, repaired, and cleared (collectively called proteostasis) weaken across many tissues over time. NIA is essentially asking investigators to test whether age-related breakdowns in peripheral proteostasis can drive, accelerate, or otherwise shape changes in the brain that lead to cognitive decline, dementia, and AD, especially in the more common sporadic form of the disease where the initiating causes are less clearly defined than in familial AD.

The scientific rationale described in the announcement contrasts well-established mechanisms in familial Alzheimer s with the uncertainty surrounding sporadic Alzheimer s. In familial AD, mutations in genes such as APP are linked to abnormal amyloid processing and aggregation, and tau pathology is often associated with hyperphosphorylation and the formation of neurofibrillary tangles. Sporadic AD, however, is strongly associated with aging itself rather than single high-penetrance mutations. Because proteostasis becomes less efficient with age in essentially all tissues, the FOA highlights a plausible body-to-brain connection: peripheral failures in protein quality control may influence systemic inflammation, metabolic and endocrine signaling, immune responses, circulating proteotoxic species, or other cross-tissue communication pathways that ultimately affect neuronal health and vulnerability. The funding opportunity is designed to move beyond a brain-only view of AD and encourage mechanistic studies that can establish causal links between peripheral proteostasis decline and brain aging outcomes.

Administratively, this was a discretionary NIH research grant using the R01 mechanism, and it explicitly did not allow clinical trials. That means the supported projects were expected to be preclinical or mechanistic human studies that do not meet the NIH definition of a clinical trial, rather than interventions that prospectively assign people to treatments to measure health outcomes. The opportunity was issued under Funding Opportunity Number RFA-AG-18-020, within the health funding activity area (CFDA 93.866). The posting was created on October 25, 2017, and the original application due date (closing date) was February 9, 2018. The public listing did not specify an award ceiling or the expected number of awards.

Eligibility for applicants was broad and included many types of U.S. organizations and governmental units, along with certain non-U.S. entities. Eligible applicants included state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; Native American tribal governments (federally recognized); tribal organizations that are not federally recognized governments; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (as long as they are not institutions of higher education in those categories); for-profit organizations (other than small businesses); and small businesses. The announcement also explicitly noted additional eligible 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, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities, including foreign organizations. In practical terms, NIA was signaling that it wanted strong multidisciplinary proposals wherever the expertise exists, including institutions serving underrepresented populations and international teams when appropriate.

In summary, this FOA targeted research that tests the hypothesis that age-related loss of protein quality control outside the brain can influence brain aging and Alzheimer s disease development. It encouraged investigators to connect peripheral proteostasis biology to neurological outcomes in a rigorous, mechanistic way, using the standard R01 research project structure while excluding clinical trials, and it made the opportunity widely accessible to academic, nonprofit, governmental, community-based, for-profit, tribal, territorial, and foreign organizations capable of carrying out the proposed science.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Role of Peripheral Proteostasis on Brain Aging and Alzheimer's Disease (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 2017-10-25.
• Applicants must submit their applications by 2018-02-09. (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.

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