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. At this time, 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, to establish research priorities and fund biomedical research in AD as well as several Alzheimer’s disease-related dementias (ADRDs).
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 frequently have different mixtures of brain pathologies, complicating both the diagnosis, as well as the treatment.
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 Opportunities
Published and Planned Funding Opportunities for Fiscal Year 2024
We are excited to share with you the research concepts approved by NINDS Council for fiscal year 2024. Periodic updates with links will be added when funding opportunities are published. They are also announced via our email listserv. Please email Kiara Bates (kiara.bates@nih.gov) to join the NINDS AD/ADRD listserv.
Please note that an approved concept listed below does not necessarily indicate an award mechanism or funding allocation is imminent or will happen. The funding opportunity is only official when published in the NIH Guide.
RE-ISSUES
Early-Stage Therapy Development for ADRD - 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
Genome Editing for ADRD - 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 - 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
Neuropathological Assessment of TBI-related Neurodegeneration and Neurocognitive Decline - 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
PET ligand development for the ADRDs - 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
NEW CONCEPTS
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
Multi-target validation for ADRD - 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 - 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 - 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 - 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 - 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 - 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
Anti-amyloid efficacy in populations with vascular risk factors of cognitive impairment and dementia - 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. Contact PO: Rebecca Hommer
TRAINING
NINDS Institutional AD/ADRD Research Training Program 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. Contact PO: Stephen Korn
NINDS Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) Advanced Postdoctoral Career Transition Award to Promote Diversity 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, 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 in order to help awardees launch competitive, independent research careers. Contact PO: Amelie Gubitz
Published Funding Opportunities for Fiscal Year 2023
RE-ISSUES
Treatments for Lewy Body Dementias and Frontotemporal Degeneration - Exploratory Clinical Trial (U01 Clinical Trial Required) RFA-NS-22-056. This Funding Opportunity invites applications from investigators seeking to conduct exploratory clinical trials designed to test new treatments for patients with Lewy Body Dementia (LBD) or Frontotemporal Dementia (FTD). Applicants may propose to conduct either Phase I or Phase II clinical trials depending on the developmental stage of the potential therapeutic, but all trials must include patients with either LBD or FTD.
Functional Target Validation for Alzheimer's Disease-Related Dementias (ADRDs) (R61/R33 Clinical Trial Not Allowed) RFA-NS-22-055. This FOA invites applications that propose the comprehensive functional validation of newly identified therapeutic target candidates for ADRD. This FOA seeks to promote critical target validation approaches to help de-risk subsequent translational research and accelerate the advancement of novel therapies for ADRD.
Structural Biology of Alzheimer's Disease Related Dementias (ADRDs) Proteinopathies (R01 Clinical Trial Not Allowed) PAR-22-208. The purpose of this FOA is to continue to support studies that characterize the structure of protein aggregates found in an ADRD such as alpha-synuclein, Tau, TDP-43, TMEM106B, and FUS at a high, atomic-level resolution, using approaches such as cryo-electron microscopy (cryo-EM), cryo-electron tomogragraphy (cryo-ET), and nuclear magnetic resonance (NMR) spectroscopy.
TRAINING
Training Award to Promote Cross-Training in the Fields of Traumatic Brain Injury (TBI) as a Risk Factor for Alzheimer’s Disease/Alzheimer’s Disease Related Dementias (AD/ADRD) (K18 Clinical Trial Not Allowed) RFA-NS-22-061. This funding opportunity encourages applications for short-term (1 year) mentored career enhancement awards to further understand TBI as a risk factor for AD/ADRD.
NEW CONCEPTS
Cellular and Molecular Mechanisms of Prion-Like Aggregate Seeding, Propagation, and Neurotoxicity in AD/ADRD PAR-23-023. This purpose of this Funding Opportunity Announcement (FOA) is to solicit applications that propose mechanistic studies in animal, cell culture, and/or human tissue models to elucidate the mechanisms by which prion-like processes in AD/ADRD are initiated, propagated, and ultimately lead to neurodegeneration and circuit dysfunction.
AD/ADRD, Adverse Childhood Experiences, and Social Determinants of Health Ancillary Studies of Existing Longitudinal Cohorts (R01 - Clinical Trial Not Allowed) PAR-22-221. The purpose of this FOA is to support studies that expand the use of existing data resources to drive new discoveries that can lead to better understanding of the relationship between early life social determinants of health, adverse childhood experiences, AD/ADRD biomarkers, and the development of cognitive impairment and dementia, especially in populations experiencing health disparities.
Early-Stage Therapy Development for ADRD RFA-NS-22-059. This FOA encourages early-stage development of novel small molecule or biologic therapeutics for NINDS mission-relevant ADRD. This FOA covers four stages of early therapy discovery/development with each stage gated by go/no-go milestones. Applicants may enter the program at the stage appropriate to their research. The R61 phase supports preparatory research stages 1 -3: 1) development of in vitro and/or ex vivo assays that can support therapeutic screening efforts, 2) screening efforts to identify and characterize potential therapeutic agents, and 3) therapeutic optimization, pharmacodynamic and pharmacokinetic studies. The R33 phase supports stage 4, in vivo efficacy studies in an animal model of disease. This FOA supports 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.
Pragmatic Clinical Trials in Community Settings to Decrease or Prevent VCID Outcomes, Including in Populations that Experience Health Disparities (U01 Clinical Trial Required) RFA-NS-23-001. The purpose of this FOA is to solicit applications for pragmatic clinical trials to decrease or prevent negative clinical outcomes due to VCID, including locally representative NIH defined populations that experience health disparities in dementia.
Tools and resources to understand the vascular pathophysiology of in vivo neuroimaging findings in TBI-related dementia and/or VCID (U24 - Clinical Trials Not Allowed) RFA-NS-23-002. Promote in-depth, post-mortem pathological examination and analysis, in combination with analysis of cellular, molecular, and pre- and post-mortem MRI data, of brain lesions resulting from TBI and/or dysfunctional vasculature or vascular processes, such as white matter hyperintensities, infarcts (including cortical microinfarcts), and microbleeds as they relate to postmortem pathology of AD/ADRD.
Impact of the Microbiome-Gut-Brain Axis on Alzheimer's Disease and Alzheimer's Disease-Related Dementias (R01 Clinical Trial Not Allowed) PAR-22-211. This FOA invites applications for basic and translational research on the impact of the microbiome on an AD/ADRD.
Connecting Machine Readable Digital Human AD/ADRD Neuropathological Library Platforms for Advanced Analytics (U24 Clinical Trial Not Allowed) RFA-NS-22-062. The purpose of this AD/ADRD initiative is to 1) develop tools, standards, and an Open-source software platform that enables a federated (multiple data repository sites with a single access portal) approach for data sharing and analysis of human digital neuropathological slides and 2) perform software testing to validate and verify that the software and tools developed can be used to perform multisite neuropathological analyses using a federated approach. slides.
Optimization of Genome Editing Therapeutics for Alzheimer’s Disease-Related Dementias RFA-NS-23-017. This FOA supports the optimization of promising genome editing-based therapeutic leads for AD/ADRD, towards IND-enabling studies.
Blood Brain Barrier Response to Antibodies Targeting Beta-Amyloid (R01 - Clinical Trial Not Allowed) PAR-22-235. This FOA solicits applications designed to increase understanding of cellular and molecular mechanisms that can be targeted to protect the blood-brain barrier, and thus brain blood vessels, during therapeutic interventions that target beta-amyloid.
CONCEPTS FOR SUPPLEMENTAL FUNDING
Notice of Special Interest (NOSI): COVID-19 Related Revisions to NINDS ADRD Human Subjects Cooperative Agreement Programs NOT-NS-23-001. This NINDS Notice of Special Interest (NOSI) invites applications for administrative supplements to address staffing shortages that are significantly impacting the recruitment of participants for NINDS administered Alzheimer's Disease / Alzheimer's Disease and RelaTed Dementias (AD/ADRD) clinical research studies.
For NINDS AD/ADRD Payline Information, see here.
NIH Estimates of Funding for Various Research, Condition, and Disease Categories
| Research/Disease Areas* | FY 2018 (Actual) |
FY 2019 (Actual) |
FY 2020 (Actual) |
FY 2021 (Estimated) |
FY 2022 (Estimated) |
|---|---|---|---|---|---|
| Alzheimer's Disease Including Alzheimer's Disease Related Dementias (AD/ADRD) |
$1,911 | $2,398 | $2,869 | $3,194 | $3,287 |
| Alzheimer's Disease | $1,789 | $2,240 | $2,683 | $2,994 | $3,079 |
| Frontotemporal Dementia | $94 | $158 | $166 | $169 | $176 |
| Lewy Body Dementia | $38 | $66 | $84 | $93 | $96 |
| Vascular Cognitive Impairment/Dementia | $259 | $299 | $362 | $368 | $382 |
*Dollars in millions and rounded
Proceedings & Outcomes
AD/ADRD Summits
The National Plan’s Goal 1 aims to prevent and effectively treat (delay onset, slow progression of) AD/ADRD by 2025. To help achieve Goal 1, and as a federal action specified in the National Plan, periodic summits are held to set and refine AD/ADRD research priorities in the National Plan. Visit the Assistant Secretary for Planning and Evaluation (ASPE) to learn more about the National Plan to Address Alzheimer’s disease.
Alzheimer's Disease-Related Dementias Summit 2022
Alzheimer's Disease-Related Dementias Summit 2019
Alzheimer's Disease-Related Dementias Research Summit 2018
Alzheimer's Disease-Related Dementias Summit 2016; Proceedings article summarizing the 2016 Alzheimer's Disease-Related Dementias Summit
Alzheimer's Disease-Related Dementias Research Summit 2015
Alzheimer's Disease-Related Dementias Summit Conference 2013; Proceedings article summarizing the 2013 Alzheimer's Disease-Related Dementias Conference
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
Funding Opportunities
Alzheimer's Disease and Related Dementias Funding Opportunities
News & Events
A new culprit tangles with ApoE4 in Alzheimer’s disease
Designer compound may untangle damage leading to some dementias
Alzheimer's Association International Conference
Related Topics
HHS Alzheimer Website
The US federal government's main webpage for information on Alzheimer's disease.HHS sitio web de enfermedad de Alzheimer y las demencias relacionadas
La página web principal del gobierno federal de EE. UU. para obtener información sobre la enfermedad de Alzheimer.ADRD Prioritized Research Milestones
Research priorities for ADRD are identified and updated through periodic NIH-hosted ADRD 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)National Alzheimer's Coordinating Center
A national database of standardized clinical and neuropathological research data (NIA/NIH). The standardized data and neuropathology data are collected at the NIA funded Alzheimer’s Disease Centers.Alzheimer’s Disease Research Implementation Milestone Database
Tool for tracking funding initiatives and activities aimed at achieving the Research Milestones that were developed from NIH-hosted AD and ADRD Summits.National Cell Repository for Alzheimer's Disease (NCRAD)
NCRAD is an NIA funded biorepository for Alzheimer’s Disease and Related Dementias studies. NCRAD banks a variety of biospecimens including DNA, RNA, plasma, serum, CSF, LCLs, and PBMCsThe NINDS Human Cell and Data Repository
Available cell sources currently include fibroblasts and/or induced pluripotent stem (iPS) cells.NINDS Biosend
BioSEND currently banks a variety of biospecimens including DNA, plasma, serum, RNA, CSF, and saliva from 16 different biomarker studies that focus on neurological and neuropsychiatric diseases.NINDS Human Genetics Resource Center
Housing over DNA samples and cell lines.Alzheimer's Disease Preclinical Efficacy Database (AlzPED)
AlzPED serves as a knowledge platform for the dissemination of data and analysis in a manner that promotes efficiency, transparency, reproducibility and accuracy of research aimed at preclinical therapy development for AD.Parkinson’s Disease Biomarkers Program (PDBP)
The PDBP facilitates biomarker discovery and validation efforts, leveraging broadly shared clinical and biospecimen data, with the overarching goal of improving clinical trial design and therapeutic development in PD, Lewy Body Dementia (LBD), and Parkinsonisms.NIH NeuroBioBank
Since 2013, the NIH NeuroBioBank has catalyzed scientific discovery through the centralization of resources aimed at the collection and distribution of human post-mortem brain tissue.iPSC Neurodegenerative Disease Initiative
We will create a foundational repository of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR/Cas9-based genetic engineering. Our target goals are 132 variants across 72 AD/ADRD genes, 8 of which are known AD-related genes, 15 are genes linked to Dementia with Lewy Bodies/Parkinson’s Disease, 28 genes are associated with Frontotemporal Dementia/Amyotrophic Lateral Sclerosis, and 21 are genes associated with other neurodegenerative disorders.