Disease Mechanisms Milestones
Research on Disease Mechanisms
- Disease Mechanisms: Mechanisms of vulnerability and resilience (Milestone 2.A)
Create new research programs that use data-driven, systems-based approaches to integrate the study of fundamental biology of aging with neurobiology of aging…
- FTD: Find potential drug targets for FTD (Milestone 2.AA)
Elucidate the mechanisms of cell type vulnerability and cell-intrinsic and –extrinsic effects on FTD pathogenesis, with the goal of accelerating development of therapeutic targets.
- Disease Mechanisms: Interactions of peripheral systems and brain (Milestone 2.B)
Establish new research programs that employ data-driven, systems-based approaches to understand the interaction between peripheral systems (in particular: immune, metabolic, microbiome) and the brain
- MED-LATE: Understanding mechanisms and relationships to other diseases (Milestone 2.BB)
TDP-43 in AD/ADRD: Understanding mechanisms and relationships to other diseases
- Disease Mechanisms: Epigenetics programs (Milestone 2.C)
Create research programs on epigenetics to understand how genetic and environmental factors interact across the lifespan to influence brain aging…
- MED COVID-19: Understanding AD/ADRD brain changes after COVID-19 (Milestone 2.CC)
Understanding AD/ADRD brain changes after COVID-19
- Disease Mechanisms: Sex differences (Milestone 2.D)
Create programs in basic, translational and clinical research aimed at comprehensive understanding of the impact of sex differences on the trajectories of brain aging…
- Disease Mechanisms: APOE physiology (Milestone 2.E)
Create cross-disciplinary research programs aimed at understanding the integrative physiology of APOE…
- Disease Mechanisms: Circadian rhythms and sleep (Milestone 2.F)
Create new research programs aimed at understanding the integrative physiology of circadian rhythms and sleep…
- Disease Mechanisms: Genetic data sharing (Milestone 2.G)
Maximize the translational potential of genetics research by ensuring rapid and broad sharing of large-scale genetic/genomic data...
- Disease Mechanisms: Common mechanisms (Milestone 2.H)
Continue to support cross-disciplinary research to discover and understand disease mechanisms...
- Disease Mechanisms: The microbiome (Milestone 2.I)
Enable a system biology approach to decipher the complex role of the microbiome in brain aging and AD/ADRD...
- Disease Mechanisms: Social and psychosocial factors (Milestone 2.J)
Expand research on the role of social and psychosocial factors, on AD risk and resilience to risk in ethnically and socioeconomically diverse populations...
- Disease Mechanisms: Cognitive resilience (Milestone 2.K)
Create new research programs that use data-driven, network biology approaches aimed at understanding the (epi)genetics and complex biology of cognitive resilience...
- Multiple Etiology Dementias: Facilitate basic and clinical research (Milestone 2.L)
Promote basic and clinical research in multi-etiology dementia.
- LBD: Understand Lewy body spreading and interactions with other AD/ADRD-related pathologies (Milestone 2.M)
Develop LBD animal, cellular, and in vitro models that recapitulate key features, including clinical pathophysiologic heterogeneity to identify mechanistic candidates for interventions.
- FTD Basic Mechanisms: Determine role of tau and multiple pathologies (Milestone 2.N)
Clarify the mechanism of tau pathogenesis and associated neurodegeneration.
- FTD Basic Mechanisms: Understand role of genetic mutations (Milestone 2.O)
Determine the molecular basis for C9ORF72 expansion-and GRN mutation-related neurodegeneration.
- FTD Basic Mechanisms: Characterize TDP-43 and FUS roles in FTD (Milestone 2.P)
Determine the mechanism of TDP-43 and FUS pathogenesis and toxicity.
- VCID Basic Research: Role of the neurovascular unit (Milestone 2.Q)
Encourage basic science research that investigates the impact of aging, AD pathology, and genes on peri- and para-vascular clearance mechanisms, the NVU, and cerebrovascular function.
- VCID Basic Research: Understand cerebrovascular and cardiovascular risk factors for dementia (Milestone 2.R)
Encourage basic science research that investigates the impact of cerebrovascular risk factors/genes and atherosclerosis on AD-related neurodegeneration.
- VCID Clinical Research: Determine interrelationship between VCID and AD biomarkers in humans (Milestone 2.S)
Determine interrelationships among aging, cerebrovascular disease and risk factors, resilience factors, genetic variants, amyloid, tau, and neurodegeneration.
- LBD: Effects on non-motor brain areas and cognition (Milestone 2.T)
Understanding the molecular, cellular and α-synuclein in the context of non-motor brain areas.
- TDP-43 in AD/ADRD: Determine molecular mechanisms of TDP-43-related disease (Milestone 2.U)
Determine underlying pathobiologic and molecular mechanisms of cellular TDP-43 displacement, post-translational modifications such as phosphorylation, and pathology in pre-symptomatic and manifest
- TDP-43 in AD/ADRD: Determine why TDP-43 brain pathology cccurs in both cognitively normal and cognitively impaired individuals (Milestone 2.V)
Examine the pathologic phenotype(s) of TDP-43 pathology in asymptomatic persons and those with common dementias.
- TBI in AD/ADRD: Basic and clinical research (Milestone 2.W)
Promote basic and clinical research examining the development and progression of TBI AD/ADRD neuropathologies and associated clinical symptoms.
- Disease Mechanisms: Microbiome and diet (Milestone 2.X)
Support research to evaluate the role of the microbiome on the impact of diet on AD risk/resilience.
- Disease Mechanisms: Exposome, iPSCs and animal models (Milestone 2.Y)
Support research that utilizes animal models of LOAD and iPSC-derived cerebral organoids from human donors, to understand the molecular mechanisms by which a variety of exposures (pathogens, toxicants
- FTD: Understanding different potential causes of FTD (Milestone 2.Z)
Identify overlapping pathogenic mechanisms between FTD and other neurodegenerative disorders and syndromes.