Disease Mechanisms: Mechanisms of vulnerability and resilience (Milestone 2.A)
Achieved
Timeline Start - End
2016 - 2023Research Implementation Area
Research on Disease MechanismsCreate new research programs that use data-driven, systems-based approaches to integrate the study of fundamental biology of aging with neurobiology of aging and research on neurodegeneration, AD and AD-related dementias to better understand the mechanism(s) of vulnerability and resilience in AD across all levels of biologic complexity (from cellular to population level) and to gain a deeper understanding of the complex biology and integrative physiology of healthy and pathologic brain aging.
Success Criteria
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Launch at least 6 new research programs that use data-driven, systems-based approaches to integrate AD and ADRD research with the study of the fundamental biology of aging/neurobiology of aging.
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These programs should support studies that integrate epidemiologic, genomic, and basic research to understand: the dynamic interaction between aging and neurodegeneration mechanisms underlying individual differences in trajectories of brain aging, disease risk, age-of-onset, progression and clinical presentation.
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Ensure that these integrative research studies include under-represented, minority populations and patients with extreme phenotypes, atypical presentations of AD.
Summary of Key Accomplishments
NIA has launched more than ten targeted initiatives that combine epidemiologic, genomic, and basic research and employ cutting edge technologies to gain deeper understanding of the transitions from healthy to pathologic brain aging.
In addition to leveraging data and biosamples, these programs use cell-based and animal models to tease out detailed molecular mechanisms of neurodegeneration. Some of the key questions being addressed through these programs are: a) the impact of metabolic and vascular factors on brain aging; b) the mechanisms by which neuropsychiatric symptoms influence the onset and progression of AD; c) the role of cellular senescence; and d) the nature of resilience to disease in the presence of various risk factors for AD. NIA continues to expand these avenues of research as they provide foundational knowledge necessary to inform the development of a precision medicine approach to AD treatment and prevention.
The key accomplishments summary is current as of March 2022.
Accomplishments/Implementation Activities
Funding Initiatives
- RFA-AG-13-013: Interdisciplinary Approach to Identification and Validation of Novel Therapeutic Targets for Alzheimer's Disease (R01)
- PAR-14-281: Connectomes Related to Human Disease (U01)
- RFA-AG-14-002: Optogenetic Tools for the Study of Neural Systems in Aging and Alzheimer's Disease (R01)
- PAR-15-357: Understanding Alzheimer's Disease in the Context of the Aging Brain (R01)
- PAR-15-358: Capturing Complexity in the Molecular and Cellular Mechanisms Involved in the Etiology of Alzheimer’s Disease (R01)
- RFA-AG-15-010: Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer's Disease (R01)
- RFA-AG-16-004: Lifespan Human Connectome Project: Aging (U01)
- PAR-17-047: Selective Cell and Network Vulnerability in Aging and Alzheimer’s Disease (R01)
- PAR-18-706: Selective Cell and Network Vulnerability in Aging and Alzheimer’s Disease (R01)
- RFA-AG-17-009: Impact of Aging in Human Cell Models of Alzheimer’s Disease (R01)
- RFA-AG-17-010: From Association to Function in the Alzheimer’s Disease Post-Genomics Era (R01)
- RFA-AG-18-026: From Association to Function in the Alzheimer’s Disease Post-Genomics Era (R01)
- RFA-AG-17-057: Systems Biology Approaches to Alzheimer’s Disease Using Non-mammalian Laboratory Animals (R01)
- RFA-AG-17-061: Interdisciplinary Research to Understand the Complex Biology of Resilience to Alzheimer’s Disease Risk
- RFA-AG-18-029: Interdisciplinary Research to Understand the Complex Biology of Resilience to Alzheimer’s Disease Risk
- PAR-18-596: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01)
- NOT-AG-18-001 (#6): Deciphering the Glycosylation Code of Alzheimer’s Disease
- NOT-AG-18-001 (#9): Neuropsychiatric Symptoms in Alzheimer's Disease (NPS-AD)
- RFA-AG-18-021: Systems Biology Approaches using Non-Mammalian Laboratory Animals to Uncover Causes of Neurodegeneration that Might Underlie Alzheimer’s Disease and Related Dementias (R01)
- RFA-AG-18-023: Pathogenesis of Age-related HIV Neurodegeneration (R01)
- RFA-MH-19-510: Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R01)
- RFA MH-19-511: Novel Mechanism Research on Neuropsychiatric Symptoms (NPS) in Alzheimer's Dementia (R21)
- PAR-17-038; reissued as PAR-18-029: Clarifying the Relationship between Delirium and Alzheimer’s Disease and Related Dementias (R01 Clinical Trial Optional)
- PAR-17-037; reissued as PAR-18-181: Clarifying the Relationship between Delirium and Alzheimer’s Disease and Related Dementias (R21/R33 Clinical Trial Optional)
- PAR-18-519: Sensory and Motor System Changes as Predictors of Preclinical Alzheimer’s Disease (R01)
- RFA-AG-19-027: A Census of Cells and Circuits in the Aging Brain (R01)
- RFA-AG-20-041: Regulation of Brain Regional and Cell Type Specific Proteome Dynamics in Alzheimer’s Disease (R21/R01)
- RFA-AG-20-042: Regulation of Brain Regional and Cell Type Specific Proteome Dynamics in Alzheimer’s Disease (R21/R01)
- RFA-AG-20-040: Oscillatory Patterns of Gene Expression in Aging and Alzheimer’s Disease (R01)
- RFA-AG-20-025: Understanding Senescence in Brain Aging and Alzheimer’s Disease (R01)
- RFA-AG-21-010: Glial Plasticity in the Aging Brain (R01)
Research Programs and Resources
- AMP AD Target Discovery and Preclinical Validation Project
- Molecular Mechanisms of the Vascular Etiology of Alzheimer's Disease (M²OVE-AD) Consortium
- NIH Blueprint for Neuroscience Research – Human Connectome Project
Research Highlights
- Workshop: Neuroscience Blueprint (BP) symposium on “Connectome Celebration: Human Connectome Project 2.0” (2016)
- Workshop: Role of Glycosylation and Carbohydrates in Aging and Early AD Pathogenesis (2018)
- Workshop: Disruptive Approaches to Understand the Initiation and Transmission of Misfolded Proteins in Alzheimer’s Disease (AD) (2016)
- Workshop: NIA/VA Partnership Meeting on Traumatic Brain Injury as Risk Factor for Alzheimer’s Disease (AD) and AD Related Dementias. Feb 26-27, 2019
- Workshop: Senescence in Brain Aging and Alzheimer’s Disease. September 18-19, 2019, Bethesda MD