New Model of Brain Cell-Blood Vessel Interaction Can Help Study Alzheimer’s

Learn about a new 3D model of the neurovascular unit which helps to study how the vasculature contributes to neurodegenerative disease.

What: A new 3D model of the neurovascular unit – complex structure of brain cell/blood vessel interaction – helps to study how the vasculature contributes to neurodegenerative disease and affects the accumulation of tau and amyloid-beta peptides in Alzheimer’s disease (AD).

Where: Robert J, et al. “An In Vitro Bioengineered Model of the Human Arterial Neurovascular Unit to Study Neurodegenerative Diseases,” Molecular Neurodegeneration, 2021

BrightFocus Connection: This project was supported by an Alzheimer’s Disease Research (ADR) postdoctoral fellowship grant to first author Jérôme Robert, PhD, while at the University of British Columbia (UBC) and the Institute of Clinical Chemistry. He is currently at the University Hospital of Zurich. Senior author Cheryl Wellington, PhD, was his mentor on the grant and is a member of the ADR Scientific Review Committee. She is a professor of Pathology and Laboratory Medicine at UBC.

Why It Is Important: Scientists have designed several animal models of neurodegeneration focusing on changes in blood flow from brain capillaries. But these models are limited in their ability to study how cerebral arteries interact with various brain cells and affect neuronal function. In this proof-of-concept study, the researchers designed the first 3D model to study how changes in the vasculature can contribute to brain pathology associated with Alzheimer’s disease including the buildup of toxic proteins and neurodegeneration.

The team used bioengineering techniques to design a 3D model replicating the multi-layer structure that makes up the neurovascular unit. The model includes several cell types that comprise large cerebral arteries, including the endothelial barrier that regulates exchanges in the bloodstream, as well as several brain cell types, including neurons and support cells that form the barrier between the brain and blood.

A major feature of the 3D model is the functional neurons derived from reprogrammed human skin cells. Unlike previous models, the neurons can elicit electrical responses and release neurotransmitters, such as glutamate. Researchers could also study neuronal responses for up to 21 days and in the future, can modify the system to include cell types derived from people with different diseases.

There is strong potential for using the 3D model to study neurodegeneration associated with AD. In addition, study results suggest the model could be a versatile research tool to study many different diseases and pathological processes in separate brain vs. blood compartments to see how the two interact and influence one another.