VCID Research: Establish new experimental models and imaging methods

AD-Related Dementias Focus

Establish and refine experimental models and technologies to identify disease-relevant mechanisms underlying VCID.

2027 RFA-NS-19-027: Human Three-Dimensional Cell Model Systems for Alzheimer's Disease-Related Dementias (ADRDs) (UG3/UH3) PAR-19-167: Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33) NOT-NS-21-038: Hyperacute MRI Imaging Studies to Understand How Brain Changes Affect AD/ADRD-Relevant Trajectories and Outcomes Post-Stroke NOT-NS-21-039: Innovative Approaches or Technologies to Investigate Regional, Structural and Functional Heterogeneity of CNS Small Blood and Lymphatic Vessels in AD/ADRD PAR-22-026: Selectively Target Technology Development to Understand How Changes or Dysfunction at the Capillary, Arterioles, and Small Lymphatic Vessels Level Can Have Long-term Impact on AD/ADRD (R01 Clinical Trial Not Allowed) PAR-23-154: Development and Validation of Models for Alzheimer’s Disease-Related Dementias (ADRD) (R61/R33 - Clinical Trial Not Allowed) RFA-NS-24-011: Center without Walls for PET Ligand Development for Alzheimer's disease-related dementias (ADRDs) (U19 - Clinical Trial Optional) (Reissue of RFA-NS-19-014) RFA-NS-24-032: Development and Validation of Human Cellular Models for Alzheimer's Disease-Related Dementias (ADRD) (R01 - Clinical Trial Not Allowed) 4.R In Progress Develop models that: reproduce small vessel disease; are relevant to VCID and AD; address white and grey matter VCID; or include genetic and acquired VCID. Verify models, including via imaging. DN 2016 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID), Including Vascular Cognitive Impairment and Vascular Dementia (VCID) Focus Area 1: Basic Mechanisms and Experimental Models, Recommendation 1 (PDF, 901K) 2022 ADRD Summit: Vascular Contributions to Cognitive Impairment and Dementia (VCID) Milestone 1, Priority 1 Translational Tools, Infrastructure, and Capabilities Human Three-Dimensional Cell Model Systems for Alzheimer's Disease-Related Dementias (ADRDs) (UG3/UH3) Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (ADRD) (R61/R33) Select projects funded in FY21 Select projects funded in FY22

  • Establish at least 2 new small vessel VCID animal models suited for VCID and mixed dementias of aging research that reproduce small vessel disease and other key pathogenic processes thought to result in human VCID.
  • At least two new in vitro models to study specific molecular mechanisms of VCID that are not feasible in animal models.
  • At least one new project to develop new imaging and other tools that can be used to better understand mechanisms of VCID etiology.

Summary of Key Accomplishments

Damage to the brain’s blood vessels is associated with increased risk for many types of dementia. To better understand this phenomenon, an NIH-funded study is currently validating new mouse models for small blood vessel disease that mimic key hallmarks of the disease. In a separate effort, researchers recently created a different type of model where cells collected from skin or blood of people with increased risk of dementia were reprogrammed to become cells found at the blood brain barrier. These patient-derived cells can thrive in a 3D life-like environment and go on to develop blood vessel-like structures. Researchers used the patient-derived cells to study how specific genetic backgrounds and cell types impact the likelihood of developing problems, such as cerebral amyloid angiopathy (CAA). Both of these models will be useful for a wide range of studies that could move dementia science closer to finding new therapies with potential to prevent or delay vascular contributions to cognitive impairment and dementia (VCID).

The key accomplishments summary is current as of July 2022.