Role of Astrocytes in Degeneration of the Neurovascular Unit in AD/ADRDs (R01 Clinical Trial Not Allowed) | PAR 22 037

Opportunity Information: Apply for PAR 22 037

This NIH grant opportunity (PAR 22-037) supports R01 research projects aimed at clarifying how astrocytes contribute to degeneration of the neurovascular unit in Alzheimer’s disease and related dementias (AD/ADRDs), with a specific emphasis on basic and mechanistic work rather than clinical trials (the funding announcement explicitly states "Clinical Trial Not Allowed"). The central idea behind the opportunity is that the neurovascular unit, which includes brain endothelial cells, pericytes, vascular smooth muscle cells, neurons, astrocytes, microglia, and extracellular matrix components, is involved in multiple biological pathways that can drive neurodegeneration. Within this system, astrocytes stand out as especially important because they sit at the crossroads of blood-brain barrier regulation, neuronal support, inflammatory and stress responses, and the brain’s reaction to injury and accumulating pathology. Because astrocytes physically and functionally interface with both blood vessels and neurons, they are positioned as promising therapeutic targets, but the field still lacks a clear, causal, mechanistic understanding of what astrocytes are doing in the neurovascular unit during health, aging, and disease.

A major motivation for the program is a recognized knowledge gap: while astrocytes are known to influence blood-brain barrier integrity and participate in APOE-related signaling (highly relevant given APOE’s strong genetic linkage to AD risk), their precise mechanistic roles in neurovascular dysfunction across the AD/ADRD spectrum remain poorly defined. This includes their potential involvement in vascular contributions to cognitive impairment and dementia (VCID), a broad category that captures how cerebrovascular disease and blood flow, vessel integrity, and barrier breakdown can contribute to cognitive decline either independently or alongside classic AD pathology. The announcement frames this gap as a clear opportunity for targeted investment, and it is described as the first NIH initiative specifically focused on the fundamental role of astrocytes in AD/ADRD, signaling an intent to stimulate a critical mass of work in this area and build a stronger mechanistic foundation for future therapies.

From an administrative and funding standpoint, the mechanism is a discretionary NIH research grant (R01) in the health area, associated with CFDA numbers 93.853 and 93.866. The listed award ceiling is $500,000, and the original closing date provided in the source data is 2022-02-04. The opportunity is open to a wide range of applicant organizations, including state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized tribal governments; tribal organizations that are not federally recognized; public housing and Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses, among others. The announcement also highlights additional eligible applicant categories often emphasized in NIH participation goals, 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, U.S. territories or possessions, regional organizations, eligible federal agencies, and even non-U.S. entities (foreign organizations).

In practical terms, the research this call is trying to catalyze is work that explains "how" and "why" astrocytes drive neurovascular unit breakdown or dysfunction in AD/ADRDs and VCID-relevant conditions, and how those astrocyte-driven changes relate to downstream neuronal injury, cognitive decline, and disease progression. The emphasis on mechanism implies projects may focus on astrocyte interactions with blood-brain barrier components, astrocyte-mediated inflammatory signaling, metabolic and trophic support roles, effects on vascular tone and cerebral blood flow regulation, and the ways astrocytes respond to or amplify pathology linked to APOE and other AD/ADRD risk factors. The overall goal is to move beyond association and toward causal explanations that can reveal testable therapeutic strategies centered on astrocyte biology within the neurovascular unit.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Role of Astrocytes in Degeneration of the Neurovascular Unit in AD/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 2021-09-30.
• Applicants must submit their applications by 2022-02-04. (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 22 037

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: