Notice of Special Interest: Innovative Approaches or Technologies to Investigate Regional, Structural and Functional Heterogeneity of CNS Small Blood and Lymphatic Vessels in AD/ADRD
First Available Due Date:
May 05, 2021
May 06, 2021
PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
RFA-NS-18-003 - Innovative Approaches or Technologies to Investigate Regional, Structural and Functional Heterogeneity of CNS Small Blood and Lymphatic Vessels (R01)
RFA-NS-18-004 - Human Studies of Target Identification, Biomarkers and Disease Mechanisms Specific to CNS Small Blood and Lymphatic Vessels (R01)
National Institute of Neurological Disorders and
The purpose of this one-year administrative supplement is to provide support for currently active awards funded under the Blueprint RFAs on the Neurobiology of Small Blood and Lymphatic Vessels (RFAs NS-18-003 and NS-18-004), or other NINDS awards with NINDS approval prior to submission of the supplement application, to advance the mechanistic understanding and/or the development of new technologies to investigate changes in brain small vessels that can lead to Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD). AD/ADRD includes Alzheimer's Disease (AD), Vascular contributions to Cognitive Impairment and Dementia (VCID), Frontotemporal Degeneration (FTD), Lewy Body Disease (LBD), and/or Mixed-Etiology Dementia (MED). Besides larger vessels such as the carotid and middle cerebral arteries that are often blocked in ischemic stroke, arterioles, venules, capillaries and lymphatic microvessels are also required for brain homeostasis and normal cognitive function. Indeed, occlusion of just one penetrating arteriole has been shown to cause brain infarcts and cognitive deficits; microvascular changes are associated with white matter hyperintensities in VCID and FTD; and microvascular changes related to blood-brain barrier damage and cerebral microbleeds are key substrates of dementia after stroke injury. And yet, despite such associations, the specific mechanisms by which small vessels of the CNS contribute to AD/ADRD-relevant pathologies remain largely unknown. There is also conflicting information in the literature regarding whether small vessel dysfunction might be a primary causal factor in AD/ADRD etiologies or a secondary consequence of other disease processes (i.e. such as the accumulation of toxic protein aggregates or hypertension). Furthermore, the poor accessibility of small vessels in the brain is a major barrier to research in this area and new technologies are desperately needed to overcome current limitations in the imaging of the small cerebrovasculature and in monitoring their function and role in disease and repair processes. To further stimulate research in these areas, we are soliciting administrative supplement applications that address some of these topics. Examples of areas of interest include:
- The extension of ongoing mechanistic studies into an AD/ADRD-relevant animal or cell culture model.
- The incorporation of mechanistic studies to determine how small blood or lymphatic vessels interact with, are changed by, and/or regulate the clearance of AD/ADRD-relevant protein aggregates.
- The addition of cognitive testing or cognitive functional outcomes to ongoing studies, with the goal of correlating to changes in small blood or lymphatic vessels.
- The extension of ongoing human imaging studies of brain small vessels into an AD/ADRD-relevant patient population.
- The addition of new neuroimaging to ongoing animal studies that would better inform underlying mechanisms of small vessel dysfunction that contribute to cognitive impairment and other AD/ADRD-relevant pathologies.
- Development and/or testing of new technologies to allow improved visualization and/or functional monitoring of small blood and lymphatic vessels in AD/ADRD relevant populations or animal models.
As with all administrative supplements, the work proposed must be within the scope of the already funded research project. If an investigator is unsure whether their supplemental project would be considered within scope, then they should contact the appropriate program officer to discuss the proposed studies. Finally, as with the original RFAs, supplement applications focused on large blood vessels,diseases of large blood vessels,or small blood and lymphatic vessels in peripheral organs will be considered out of scope for this NOSI..
Application and Submission Information
Applications for this initiative must be submitted using the following opportunity or its subsequent reissued equivalent.
- PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)
All instructions in the SF424 (R&R) Application Guide and PA-20-272 must be followed, with the following additions:
- Application Due Date(s) – May 5, 2021, by 5:00 PM local time of applicant organization.
- For funding consideration, applicants must include “NOT-NS-21-039” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B may not be considered for this initiative.
- Eligibility Criteria
- Existing awardees of the FOAs listed below are eligible to apply:
- RFA-NS-18-003 "Innovative Approaches or Technologies to Investigate Regional, Structural and Functional Heterogeneity of CNS Small Blood and Lymphatic Vessels (R01)"
- RFA-NS-18-004 "Human Studies of Target Identification, Biomarkers and Disease Mechanisms Specific to CNS Small Blood and Lymphatic Vessels (R01)"
- Awards issued by the NINDS under other funding opportunity announcements (FOAs) if the request is approved by the NINDS prior to the submission of the supplement application.
- Requests may be for one year of support only.
- Application budgets must reflect the actual needs of the proposed project. Supplement budget requests may not exceed $133,000 in direct costs per year or 100% of the direct costs of the current year of the parent award (exclusive of Facilities and Administrative costs on sub-contracts), whichever amount is lower. Applications that want to propose higher budgets must receive permission from the project officer and IC Contact prior to submission.
- Applicants cannot apply for more than one supplement to a given parent grant/award.
- The Research Strategy section of the application is limited to 6 pages.
- The application Abstract section should clearly describe the proposed supplement and state its relevance to AD/ADRD. The Research Strategy section should also include a summary or abstract of the funded parent award, as well as a separate subsection that explains the relevance of the supplement research to both the parent award and AD/ADRD.
- Applicants are strongly encouraged to notify the program contact at the Institute supporting the parent award that a request has been submitted in response to this NOSIin order to facilitate efficient processing of the request
- The process for Streamlined Submissions using the eRA Commons cannot be used for this initiative.
NINDS will conduct administrative reviews of all applications. In addition to all requirements outlined in the original FOA that the parent award was submitted under, the following questions will be used during the review process. NIA will make funds available to NINDS for the funding of meritorious applications, provided that sufficient funds are available.
Administrative Review Questions:
- Is the work proposed within the scope of the active award?
- Is the work proposed focused on AD/ADRD?
- Is the proposed project rigorous and transparent?
- Is the work likely to have a sustained impact on our understanding of the role of CNS small blood or lymphatic vessels in pathogenesis and/or progression of the AD/ADRD?
- Is the work likely to stimulate additional related activities leading to progress in the field of AD/ADRD research?
Please direct all inquiries to:
Dr. Francesca Bosetti
National Institute of Neurological Disorders and Stroke (NINDS)