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The purpose of this notice of funding opportunity (NOFO) is to support research that 1) defines associations between variations in human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genetic regions and immune-mediated diseases, 2) elucidates mechanisms underlying these associations with the goal of advancing therapeutic opportunities, and/or 3) validates association data in order to improve the predictive power of clinical disease screening.

This NOFO will solicit R01 applications that propose studies in animal, cell culture, and/or human tissue models to elucidate the mechanisms by which COVID-19 interacts with and/or modulates AD/ADRD-relevant phenotypes. Either the model itself or the experimental readouts will be required to incorporate AD/ADRD risk factors, pathologies, or relevant comorbidities. To this end, proposals can focus on one or more of the following: - Mechanistic studies that address how COVID-19 impacts CNS pathology and cognitive outcomes when AD/ADRD pathology is already present (for example, in a model of AD/ADRD). - Mechanistic studies that address how COVID-19 accelerates AD/ADRD pathology and cognitive deficits in a prodromal model (early phase, pre-symptomatic). - Mechanistic studies that address how COVID-19 predisposes for AD/ADRD and/or interacts with relevant comorbid conditions and risk factors (cellular mechanisms that could potentially increase the risk for future AD/ADRD).

This initiative is designed to promote discovery of cellular and molecular mechanisms that underlie brain blood vessels responses to passive anti-beta-amyloid immunotherapy that result in amyloid-related imaging abnormalities (ARIA). The goal is to establish an understanding of molecular mechanisms that can be targeted to protect the blood brain barrier (BBB), and thus the brain blood vessels, during therapeutic interventions that target beta-amyloid.

(Reissue of RFA-NS-16-021, PAR-18-413, RFA-NS-19-039) Diffuse brain white matter disease is highly prevalent in the elderly, and has been clinically associated with vascular contributions to cognitive impairment and dementia (VCID) in both men and women. Diffuse white matter disease is thought to include a variety of pathologies including demyelination and/or fiber loss due to multifocal infarction and local ischemia. It is often accompanied by arteriosclerosis in deep penetrating arteries, multiple infarcts in the basal ganglia, brainstem or cerebellum. Though most commonly extending out from the periventricular surfaces, it may also occur in subcortical white matter. Diffuse white matter disease is typically detected in clinical settings as hyperintensity on magnetic resonance imaging (MRI) or signal loss on computed tomography x-ray (CT) scan; diffuse white matter disease can be detected histologically as well, for example in human pathology and in studies using animal models. Despite the prevalence and potential significance of white matter disease for cerebrovascular disease etiology and cognitive outcomes, much remains to be learned about the cellular and molecular causes, regional vulnerability, and progression over time. The physiological consequences of diffuse white matter disease on local axon and neural circuit function are almost completely unknown. The purpose of this FOA is to address some of the many gaps in knowledge of the biologic mechanisms of the commonly occurring, cerebrovascular disease and age-related diffuse white matter disease at the molecular, cellular, tissue and brain circuit level. The ultimate goal of this fundamental research is to inform future efforts to reduce the burden of illness due to age-related vascular contributions to cognitive impairment and dementia.

This is a non-competitive funding opportunity intended to fund a single award. NCATS is announcing its intent to issue a single source cooperative agreement to Cincinnati Childrens Hospital Medical Center (CCHMC) to support the Data Management and Coordinating Center. The Rare Diseases Clinical Research Network (RDCRN) is intended to advance and improve diagnosis, management, and treatment of numerous, diverse rare diseases through highly collaborative, multi-site, patient-centric, translational, and clinical research with an emphasis on early and timely identification of individuals with rare diseases and clinical trial readiness. The DMCC facilitates and supports the activities of each individual Rare Diseases Clinical Research Consortium (RDCRC) along with trans-network activities that broadly facilitate the advancement of rare disease research via four avenues: administrative support, data management support, clinical research support and patient engagement, and broad dissemination of information. The RDCRCs will continue conducting research conducted under a separate NOFO.

This Notice of Funding Opportunity (NOFO) invites grant applications from institutions/organizations that propose to build a Medical Rehabilitation Research Center. The centers will have a specific rehabilitation research theme and be comprised of a research project supported by 3 cores. The 3 cores will have functions within the center as well as functions nationwide. Together, the cores will support: administrative functions (including an optional pilot program), resource sharing, and community engagement and outreach. The Medical Rehabilitation Research Centers will contribute tomedical rehabilitation research infrastructure by developing and disseminating techniques, data, theories, research programs, and expertise with the goal of enhancing the capability of medical rehabilitation investigators to understand mechanisms of functional recovery, develop therapeutic strategies, identify clinical care gaps, and improve the lives of people with disabilities. Applications must include a plan for inclusion of People with Lived Experience (as a required other attachment) that is relevant to the research theme of the center and increases the potential impact of the center.

The objective of this Notice of Funding Opportunity (NOFO) is to invite new and renewal applications for the Rare Diseases Clinical Research Consortia (RDCRC) that comprise the Rare Diseases Clinical Research Network (RDCRN). The RDCRCs are intended to advance and improve diagnosis, management, and treatment of numerous, diverse rare diseases through highly collaborative, multi-site, patient-centric, translational and clinical research. Special emphasis will be placed on the early and timely identification of individuals with rare diseases and clinical trial readiness.

The purpose of this Alzheimers Disease-Related Dementia (ADRD) initiative is to promote the development and distribution of innovative technologies, methods, protocols, and biomedical materials that enhance combined human neuropathology and neuroimaging research with data aimed at understanding the underlying pathophysiology of in vivo imaging results typically associated with vascular contributions to cognitive impairment and dementia (VCID) in TBI-related dementia and other ADRD diagnoses. Resources developed under this FOA must follow open data sharing practices and are intended to expand the broader research communitys capacity to perform research aimed at neuropathologically-informed understanding of the vascular pathophysiology of clinically-relevant, in vivo neuroimaging findings.

This notice of opportunity announcement (NOFO) is issued by the National Institute of Neurological Disorders and Stroke to enable submission of program project grant applications that propose to conduct innovative, interactive research to answer significant scientific questions that are important for the mission of NINDS, via a synergistic collaboration between outstanding scientists who might not otherwise collaborate. The program project grant is designed to support research in which the funding of several interdependent highly meritorious projects as a group offers significant scientific advantages over support of these same projects as individual research grants.

"Fluctuating cognition can occur in many types of dementia and is a core clinical feature of Dementia with Lewy Bodies. Cognitive fluctuations can last from seconds to days, are unpredictable (e.g., do not just occur in the evenings, as with sun-downing), and are associated with poor daily functioning for the patient. A number of small studies have suggested that cognitive fluctuations in subjects with dementia may be related to epileptiform discharges and impaired oscillatory activity on EEG, but it is not clear that these are the only factors involved in patient populations that often experience dysautonomia, orthostasis, and sleep disturbances. The etiology of cognitive fluctuations may be multi-factorial and may vary in different dementia populations. Understanding the physiology related to cognitive fluctuations is a critical next step to the development of treatment approaches and improving quality of life for these patients. This initiate would encourage research that will better characterize the physiology responsible for cognitive fluctuations in ADRD populations. Given their variable appearance and time course, it is anticipated that wearable digital devices will be important for capturing fluctuations in a timely fashion, and applicants should consider incorporating those device(s) capable of acquiring the relevant data to support the hypothesized mechanism(s). Applicants may focus on assessing multiple mechanisms in a specific ADRD population, or may chose to compare mechanisms across multiple types of ADRDs. "