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