Focus on Alzheimer's Disease and Related Dementias

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What is AD/ADRD?

Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) refers to the most common forms of dementia. Dementia likely affects more than 6 million people in the U.S. and more than 55 million people worldwide. Currently, there are no known treatments to prevent or stop the progression of dementia. The toll on individuals, caregivers and society is enormous and will increase as the population ages unless effective interventions are developed. NINDS collaborates with NIH’s National Institute on Aging (NIA), the lead NIH Institute for Alzheimer’s disease (AD) research and for NIH's response to the National Plan to Address Alzheimer’s Disease, to establish research priorities and fund biomedical research to decrease the burden of dementia on individuals, families, and communities. 

While AD is the most common dementia diagnosis, ADRDs share many cognitive and pathological features with and can be difficult to distinguish from AD. In fact, more often than not, patients with a clinical diagnosis of Alzheimer’s disease have different mixtures of brain pathologies, complicating both the diagnosis, as well as treatment. A special video testimonial to raise awareness of the disease burden on patients with AD/ADRD and their caregivers titled “Voices of AD/ADRD” was presented at the NINDS ADRD Summit 2022, and can be viewed here:

The ADRDs include:

Going forward, NINDS and NIA will continue to partner in AD/ADRD research planning and implementation, and we urge the research community to join in our efforts to accelerate scientific progress toward reducing the enormous burden and cost of dementia.

Funding Opportunity Announcements

Planned and Current Notices of Funding Opportunity (NOFOs)

 

Currently Active Funding Opportunities


Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD, and other ADRDs (R01 - Clinical Trial Not Allowed) PAR-24-148 - This initiative aims to establish deeper mechanistic insight and causal relationships between TDP-43 pathology and phenotypic outcomes, as well as mechanistic interactions between TDP-43 and other ADRD-relevant co-pathologies that may impact its regulation and function. Additionally, this concept aims to compare TDP-43 proteinopathies, including limbic-predominant age-related TDP-43 encephalopathy (LATE), with or without Alzheimer’s disease neuropathologic change (AD-NC), and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP), to further understand distinct and overlapping mechanisms in these syndromes. Due dates: June 04, 2024 and October 04, 2024 Contact PO: Linda McGavern

Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed)  PAR-24-147 The goal of this initiative is to investigate relevant Alzheimer’s Disease Related Dementias (ADRD) co-pathologies (e.g., tau, alpha-synuclein, TDP-43, TMEM106B, vascular), with optional risk factors and co-morbidities, in the same model system to identify cellular and molecular mechanisms of how multi-pathology interactions drive worsening neurodegenerative processes and ADRD phenotypic outcomes. Due dates: June 04, 2024 and October 04, 2024 Contact PO: Linda McGavern

Efficacy and Safety of Amyloid-Beta Directed Antibody Therapy in Mild Cognitive Impairment and Dementia with Evidence of Both Amyloid-Beta and Vascular Pathology (U01 - Clinical Trial Required) (RFA-NS-24-013) - The goal of this initiative is to encourage the development and implementation of a phase 3 clinical trial to determine the efficacy and safety of FDA approved monoclonal antibody therapy in mixed-etiology dementia populations with evidence of vascular contributions to cognitive impairment and dementia. Due date: May 20, 2024 Contact PO: Rebecca Hommer

NINDS Institutional AD/ADRD Research Training Program (T32 Clinical Trial Not Allowed) (PAR-22-021) - The goal of this initiative is to provide support for institutional research training programs in ADRD. A fundamental goal of this specific program will be for trainees to develop an understanding not only differences and similarities among the various AD/ADRD disorders, but more generally to develop a strong scientific and innovative orientation towards understanding the root mechanistic causes of cognitive impairment and dementia. Due date: May 25, 2024 Contact POStephen Korn

NINDS Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00 Independent Clinical Trial Not Allowed) (PAR-22-022) - The purpose of this initiative is to enhance workforce diversity by supporting a mentored research experience (K99) followed by independent research (R00) for postdoctoral fellows working in research areas supported by the AD/ADRD Initiative, including research on Alzheimer’s disease, Multiple-Etiology Dementias (MED), vascular contributions to cognitive impairment and dementia (VCID), Lewy body dementia (LBD), and frontotemporal degeneration (FTD). The program will provide independent NIH research support during this transition in order to help awardees launch competitive, independent research careers. Due date: NIH Standard dates  Contact PO: Amelie Gubitz

Administrative Supplements to Promote Diversity for NINDS AD/ADRD Awardees (NOT-NS-21-047)- This initiative is to encourages eligible NINDS awardees in the AD/ADRD research community to apply for administrative supplements in response to PA-23-189, "Research Supplements to Promote Diversity in Health-Related Research," or any reissues of this announcement through the expiration date of this Notice. Expiration date: March 31, 2024 Contact PO: Amber McCartney

Development and Validation of Human Cellular Models for Alzheimer's Disease-Related Dementias (ADRD) (R01 - Clinical Trial Not Allowed) RFA-NS-24-032- The purpose of this initiative is to develop and validate novel, complex, and pathophysiologically relevant human cellular models of Alzheimer’s Disease-Related Dementias (ADRD) to address a gap in currently available models. The cellular model systems would be expected to capture the multi-faceted pathologies and multiple cell types observed in ADRDs. Due dates: June 20, 2024 and October 21, 2024 Contact POs: Linda McGavern and Frank Shewmaker

Mechanisms of Cognitive Fluctuations in ADRD Populations (R01 - Clinical Trial Optional) RFA-NS-25-014 - This initiative invites research applications focused on understanding the underlying pathophysiology of cognitive fluctuations in people diagnosed with Alzheimer’s Disease- Related Dementias (ADRD). Contact PO: Debra Babcock


Planned Initiatives

We are excited to share with you the research concepts approved by NINDS Council for the fiscal year 2025. Please note that this page will be periodically updated with links when funding opportunities are published. These are also announced via our email listserv (to join the NINDS AD/ADRD listserv, please email kiara.bates@nih.gov ).

Please note that an approved concept listed below does not necessarily indicate an award mechanism or funding allocation is imminent or will happen. The NOFO is only official when published in the NIH Guide.


2025: Previously Published NOFOs Planned for Re-Issue

Neuropathological Interactions Between COVID-19 and ADRD- This initiative is to solicit 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 ADRD-relevant phenotypes. Proposed research must focus on ADRD interactions with COVID-19, for example by incorporating ADRD outcomes, risk factors, pathologies, or relevant comorbidities. Contact PO: William P. Daley

Mechanistic and Hemodynamic Basis of Diffuse White Matter Disease in Vascular Contributions to Cognitive Impairment and Dementia (VCID)- This initiative is designed to support hypothesis-testing research to elucidate hemodynamic, cellular, and molecular mechanisms that underlie diffuse white matter disease of vascular origin including multifocal, small, and silent brain infarcts that may contribute to cognitive impairment and dementia. Contact PO: Roderick Corriveau

Optimization of Genome Editing Therapeutics for ADRDs- This initiative will support early translational research focused on somatic cell genome editing for Alzheimer's Disease Related Dementias (ADRDs). It is expected that these studies will address the feasibility of using genome editing for therapy development for ADRDs. Contact PO: Timothy LaVaute

Functional Validation of Novel Targets in ADRD- This initiative is to provide the translational scientific community with increased confidence in the efficacy and safety of novel target to trigger customized therapeutic strategies in ADRDs. Contact PO: Pascal Laeng

Tools and resources to understand the vascular pathophysiology of in vivo neuroimaging findings in ARIA- The goal of this initiative is to encourage applications that develop and share tools and resources, including biomarkers, biomedical materials, innovative technologies, and standardized methods and protocols, that further enable combined analysis of human in vivo MRI, ex vivo MRI, and postmortem neuropathology data to understand the underlying pathophysiology of spontaneous and passive anti-Aβ monoclonal antibodies (MABs) induced Amyloid Related Imaging Abnormalities (ARIA) in AD/ADRD. Contact PO: Carlos Faraco

Protective strategies to reduce Amyloid Related Imaging Abnormalities (ARIA) after anti-Aβ immunotherapy- This initiative is to support mechanistic investigations to better understand the mechanisms underlying BBB dysfunction after anti-b-amyloid immunotherapy and studies to develop potential protective interventions to reduce severe adverse events due to ARIA, with and without specific risk factors, such as apolipoprotein E4 (APOE) carrier status. Contact PO: Francesca Bosetti


2025: New NOFO Concepts

Interaction Between Environmental Factors and Lewy Body Dementia (LBD)- This initiative is to support research that firmly establishes causal links between environmental factors and Lewy Body formation. This concept aims to reveal the mechanistic basis for how exogenous environmental factors can lead to LBD. Contac PO: David Jett

Mechanistic Investigations into ADRD associated protein structures in biological settings- This initiative is to support studies proposing to develop and/or utilize methodologies for in-cell structural biology to address questions that have previously been experimentally impossible. The applications are expected to focus on determining AD/ADRD-linked macromolecular structures in native (healthy and pathological) settings. Contact PO: George Umanah

Integrative Multi-Omic Profiling for Lewy Body Dementia- This initiative is designed to support would support research to conduct genetic and molecular characterization of LBD. This may include whole genome sequencing, longitudinal bulk-transcriptomics, longitudinal matched plasma, and cerebrospinal fluid (CSF) proteomic analysis, and post-mortem single-cell RNA sequencing, which will be generated and paired with harmonized longitudinal clinical data. Contact PO: Christine Swanson-Fischer

ADRD Risk and Disease Following Nervous System Exposures at Biological Interfaces with the Environment- This initiative is to support research that aim to by determine how exposures at innervated human surfaces affect ADRD disease mechanisms and phenotypic outcomes. These exposures include toxins and toxic chemicals, viral and other pathogens, and other environmental exposures. Contact PO: David Jett

Including ADRD Biomarker Measures and APOE Genotype Status to ADRD Human Subjects Research Studies- This initiative is to provide funding to existing AD/ADRD cohort studies to support the inclusion/addition of ADRD fluid-based biomarker measures and APOE genotype status when they are not already utilized in the original study. Contact PO: Amber McCartney

Clinical Trial Readiness to Understand and Develop Solutions to Social, Ethical, and Behavioral Implications (SEBI) Barriers to Health Equity in ADRD- This initiative is to support research that establishes clinical trial readiness for community-driven interventions to understand and develop solutions to barriers to equity in ADRD outcomes among NIH-designated populations that experience health disparities (HDPs). Contact POs: Richard T. Benson, Rebecca Hommer and Carolina Mendoza-Puccini

Safety and Efficacy of Amyloid-Beta Directed Antibody Therapy in Mild Cognitive Impairment and Dementia with Evidence of Both Amyloid-Beta and Lewy Body Dementias - The goal of this initiative is to encourage the development and implementation of clinical trials to determine the efficacy and safety of amyloid-beta clearing monoclonal antibody therapies in patients with evidence of both Alzheimer’s (amyloid-beta) pathology and clinical LBD, i.e. Parkinson’s disease dementia (PDD) and/or dementia with Lewy bodies (DLB). Contact PO: Rebecca Hommer


Training

NINDS ADRD Advanced Postdoctoral Career Transition Award- This initiative aims to support a timely transition of outstanding postdoctoral researchers with a research and/or clinical doctorate degree from mentored, postdoctoral research positions (K99) into independent, tenure-track or equivalent faculty (R00) positions in AD/ADRD research areas by providing independent NIH research support during this transition to help awardees establish independent AD/ADRD research programs. Contact PO: Amber McCartney

NINDS ADRD Advanced Postdoctoral Career Transition Award to Promote Diversity- The purpose of this initiative is to enhance workforce diversity by supporting a mentored research experience (K99) followed by independent research (R00) for postdoctoral fellows working in research areas supported by the AD/ADRD Initiative, including research on Alzheimer’s disease, mixed etiology dementias (MED), vascular contributions to cognitive impairment and dementia (VCID), Lewy body dementia (LBD), and frontotemporal degeneration (FTD). The program will provide independent NIH research support during this transition to help awardees launch competitive, independent research careers. Contact PO: Amelie Gubitz and Lauren Ullrich

Administrative Supplements to Promote Diversity for NINDS ADRD Awardees - This initiative is to encourages eligible NINDS awardees in the AD/ADRD research community to apply for administrative supplements in response to PA-23-189, "Research Supplements to Promote Diversity in Health-Related Research," or any reissues of this announcement through the expiration date of this Notice. Contact PO: Amber McCartney

Published Funding Opportunities for Fiscal Year 2024

RE-ISSUES

Early-Stage Therapy Development for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33 - Clinical Trial Not Allowed) - This initiative will encourage early-stage development of novel small molecule or biologic therapeutics for ADRD. This initiative will support research to enable competitive follow-on applications that meet the entry criteria for the Blueprint Neurotherapeutics Network, Blueprint Biologics, or other similar later-stage translational programs. Contact PO: Rebecca Roof

Optimization of Genome Editing Therapeutics for Alzheimer's Disease-Related Dementias (ADRD) (U01 - Clinical Trials Not Allowed) (RFA-NS-24-009) - This initiative will support early translational research focused on somatic cell genome editing for Alzheimer's Disease Related Dementias (ADRDs). It is expected that these studies will address the feasibility of using genome editing for therapy development for ADRDs. Contact PO: Timothy LaVaute

Blood Brain Barrier Response to Antibodies Targeting Beta-Amyloid (PAR-23-140) - 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. The goal is to establish an understanding of molecular mechanisms that can be targeted to protect the BBB, and thus the brain blood vessels, during therapeutic interventions that target beta-amyloid. Contact PO: Roderick Corriveau

Assessment of TBI-related ADRD Pathology Related to Cognitive Impairment and Dementia Outcomes (U01 - Clinical Trial Not Allowed) (RFA-NS-24-003) - This initiative will support applications for a multisite study to comprehensively characterize the neuropathological features associated with neurodegeneration and neurocognitive decline in persons with a history of traumatic brain injury (TBI). To further advance research in the area, broad sharing of clinical and neuropathological data will be a critical feature of this initiative including developing a digital resource for distribution and sharing of assessed neuropathological tissue. Contact PO: Nsini Umoh

Center without Walls for PET Ligand Development for Alzheimer's disease-related dementias (ADRDs) (U19 - Clinical Trial Optional) - The purpose of this initiative is to support a multi-center program that will apply innovative and interdisciplinary approaches to identify and validate PET radioligands for ADRD-related targets (e.g., tau, FUS, TDP43, alpha-synuclein, etc.) and pathways (e.g., neuroinflammation, autophagy, mitochondria, etc.).  Collaborations with investigators overseeing brain bank resources and/or those overseeing existing ADRD-related resources and clinical infrastructure are encouraged. Contact PO: Debra Babcock

TRAINING

 

NEW CONCEPTS

Validating digital health technologies for monitoring biomarkers in ADRD clinical trials (R61/R33 - Clinical Trials Optional) (RFA-NS-24-026) - This initiative is to enable partnerships between academics and companies that manufacture wearable digital devices (“digital health technologies (DHTs)”) to develop and validate digital biomarkers for use in monitoring biomarkers in Alzheimer's Disease Related-Dementias (ADRD).  Contact PO: Carol Taylor-Burds

Role of Environmental Stress in the Health Inequities of Alzheimer's Disease-Related Dementias (ADRD) (R01 - Clinical Trial Not Allowed) - This initiative is to increase our knowledge of how environmental stressors in lower resourced communities impact risk for ADRD.  Contact PO: David Jett and Richard T. Benson

VCID Center Without Walls for Understanding and Leveraging Small Vessel Cerebrovascular Disease Mechanisms in ADRD (R01 - Clinical Trial Not Allowed) - This initiative is to support research that will, in parallel human-based and model-based studies, advance understanding of fundamental mechanisms related to cerebrovascular disease that contribute to dementia risk and outcomes. Contact PO: Roderick Corriveau

Using Multimodal Biomarkers to Differentially Diagnose ADRDs for Clinical Trials (RFA-NS-24-001) - The purpose of this initiative is to enable multi-site clinical validation of a multimodal set of neuroimaging and biospecimen biomarkers to differentially diagnosis three or more similarly presenting neurodegenerative diseases, including at least one of the Alzheimer’s Disease and Related Dementias (ADRDs). As part of the program deliverables, investigators will be required to submit the markers and imaging protocols through the FDA’s Biomarker Qualification Program, and/or as a diagnostic device through CDRH. Contact PO: Carol Taylor-Burds

Simultaneous and Synergistic Multi-Target Validation for Alzheimer’s Disease-Related Dementias (R61/R33 Clinical Trial not allowed) - The goal of this initiative is to validate multiple targets for future therapy development for ADRDs that better reflect the complexity of disease. Successful grantees should be in position to apply for IGNITE or other similar translational grant mechanisms after the PAR award is complete. Contact PO: Rebecca Roof

Mechanistic Investigations into ADRD Multiple Etiology Dementias (PAR-23-211) - This initiative would support investigations with a minimum of two relevant Alzheimer’s Disease Related Dementias (ADRD) co-neuropathologies (e.g., tau, alpha-synuclein, TDP-43, TMEM106B, vascular), with optional risk factors and co-morbidities, to identify interactions and cellular and molecular mechanisms upstream of aggregated protein states and to determine how these early interactive multi-pathology mechanisms drive worsening neurodegenerative processes and clinical phenotypic outcomes. Contact PO: Linda McGavern

Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD, and other ADRDs (PAR-23-212) - This initiative would support studies establishing deeper mechanistic insight and causal cellular and molecular relationships between TDP-43 pathology and clinical phenotypic outcomes. Additionally, the initiative would require comparisons between Alzheimer’s Disease Related Dementias (ADRD) TDP-43 proteinopathies, such as limbic-predominant age-related TDP-43 encephalopathy (LATE), with or without Alzheimer’s disease neuropathologic change (AD-NC), and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) to further understand distinct and overlapping mechanisms in these different syndromes. Contact PO: Linda McGavern

Neuropathological Interactions Between COVID-19 and ADRD (PAR-23-214) - This initiative would solicit 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 ADRD-relevant phenotypes. Either the model itself or the experimental readouts will be required to incorporate ADRD risk factors, pathologies, or relevant comorbidities. Contact PO: William P. Daley

Development & Characterization of Experimental models of post-TBI ADRD (PAR-23-218) - This initiative is designed to support interdisciplinary teams across multiple sites aimed at developing and characterizing a variety of experimental models that can accurately reproduce the neuropathological signatures and clinically relevant neurodegenerative, biochemical, and behavioral TBI-related dementia sequelae and phenotypes as those seen in humans. Successful models will accelerate the identification of factors and mechanistic pathways contributing towards the predisposition, initiation of and development of neurodegenerative dementia post-TBI. Innovative applications reaching beyond the current AD/ADRD animal models are highly encouraged. Contact PO: Hibah O. Awwad

Development and Validation of Models for ADRD (PAR-23-154) - This initiative would support development and validation of clinically relevant models of Alzheimer’s Disease Related Dementias (ADRD). Cellular and animal models of multiple interacting pathologies, that mimic the multiple interacting risk factors and comorbidities seen in patients, and that advance key molecular pathways in a pathophysiologically relevant context will be supported. New models need to be innovative and address a gap in the currently available models. Contact POs: Linda McGavern and Rebecca Roof

 

For NINDS AD/ADRD Payline Information.  

 

NIH Estimates of Funding for Various Research, Condition, and Disease Categories

Research/Disease Areas* FY 2020
 
FY 2021
 
FY 2022
 
FY 2023
(Estimated)
FY 2024
(Estimated)
Alzheimer's Disease Including
Alzheimer's Disease Related
Dementias (AD/ADRD)
$2,869 $3,251 $3,514 $3,749 $3,767
Alzheimer's Disease $2,683 $3,059 $3,314 $3,502 $3,515
Frontotemporal Dementia $166 $164 $169 $174 $177
Lewy Body Dementia $84 $113 $118 $124 $124
Vascular Cognitive Impairment/Dementia $362 $455 $445 $461 $464

*Dollars in millions and rounded
 

Resources and Tools

Contacts

Rod Corriveau | Program Director 
roderick.corriveau@nih.gov

Sara Dodson | Senior Health Science Policy Analyst
sara.dodson@nih.gov

Amber McCartney | Scientific Project Manager
amber.mccartney@nih.gov

Arvind Shukla | Scientific Program Analyst
arvind.shukla@nih.gov

Kiara Bates | Program Specialist
kiara.bates@nih.gov

 

Related Topics 

AD+ADRD Research Implementation Milestones database
The AD+ADRD Research Implementation Milestones database is a research framework detailing specific steps and success criteria towards achieving the goal of the National Plan to Address Alzheimer's Disease: to treat and prevent AD and ADRDs by 2025. This database includes research milestones and responsive activities for the NIH triennial AD, ADRD, and Dementia Care, Services and Supports research summits.

International Alzheimer's and Related Dementias Research Portfolio
IADRP reports categories of funded research supported by public and private organizations both in the US and abroad all categorized using the Common Alzheimer's and Related Dementias Research Ontology (CADRO)

Alzheimer’s Disease-Related Dementias Summits