Endothelial Cell APOE3 Regulates Neurovascular, Neuronal, and Behavioral Function

Area of Science:

• Neuroscience
• Vascular Biology
• Genetics

Background:

• Specialized brain endothelial cells are vital for neurovascular function.
• Human apolipoprotein E3 (APOE3) is independently important for brain health.
• The role of endothelial APOE3 in brain function remains largely unknown.

Purpose of the Study:

• To investigate the impact of endothelial cell APOE3 loss on brain vascular and neural function.
• To determine if endothelial APOE3 is essential for maintaining neurovascular integrity and cognitive processes.

Main Methods:

• Developed genetically modified mice with inducible endothelial cell APOE3 knockdown (APOE3Cre+/-).
• Utilized control mice (APOE3Cre-/-) for comparison.
• Assessed neurovascular and neuronal function using biochemical, immunohistochemical, behavioral, and electrophysiological methods at 9 months of age.

Main Results:

• Loss of endothelial APOE3 led to increased brain vascular permeability.
• Reduced vessel coverage in the brain was observed in mice lacking endothelial APOE3.
• Deficits in spatial memory, fear memory extinction, and disrupted cortical excitatory/inhibitory balance were evident.

Conclusions:

• Endothelial APOE3 plays a critical role in regulating the neurovasculature.
• Endothelial APOE3 is essential for maintaining neural circuit function and normal behavior.
• These findings highlight a novel function of endothelial APOE3 in brain health.