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.