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Milestone 4.R

AD Related Dementias – Specific

Develop next‐generation experimental models and translational imaging methods for VCID.

Success Criteria

  • Establish new small vessel VCID animal models suited for VCID and mixed dementias of aging research that: (i) reproduce small vessel disease and other key pathogenic processes thought to result in human cognitive impairment, (ii) are easily applicable to research on both VCID and AD dementia, (iii) address vascular contributions to damage of both white matter and gray matter; and (iv) include genetic and acquired conditions that cause and or are associated with VCID.
  • Support development of in vitro, including cell-based, models to study specific molecular mechanisms of VCID that are not feasible in animal models.
  • Support the development of new imaging and other tools that can be used to better understand VCID etiology at the behavioral (e.g. memory-based tasks), systems (e.g. hypoperfusion, chronic blood brain barrier breakdown), network (e.g. white matter lesions and network connectivity), pathology, cellular (e.g. variations and vulnerability in the vascular tree, neurovascular unit damage), synaptic (e.g. electrical activity), and molecular (e.g. chronic inflammation) levels.

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).

This information is current as of July 2022.

Research Implementation Area
AD Related Dementias - Specific
In Progress

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