Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction

Oct 2, 2024Biomaterials

3D lab-grown human brain blood vessel model to study blood flow problems in Alzheimer's disease

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Abstract

The model demonstrates increased blood-brain barrier permeability and alterations associated with Alzheimer's disease.

Dysfunction of the blood-brain barrier is linked to the progression of Alzheimer's disease.
A three-dimensional model replicates interactions between brain cells and Alzheimer's disease features.
Co-culture of human brain cells shows dysregulation of key markers related to blood-brain barrier function.
Amyloid-beta accumulation is visualized in both neuronal and vascular areas within the model.

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The blood-brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease. This study introduces a three-dimensional (3D) self-assembled in vitro model of the human neurovascular unit to recapitulate some of the complex interactions between the BBB and AD pathologies. It incorporates primary human brain endothelial cells, pericytes and astrocytes, and stem cell-derived neurons and astrocytes harboring Familial AD (FAD) mutations. Over an extended co-culture period, the model demonstrates increased BBB permeability, dysregulation of key endothelial and pericyte markers, and morphological alterations mirroring AD pathologies. The model enables visualization of amyloid-beta (Aβ) accumulation in both neuronal and vascular compartments. This model may serve as a versatile tool for neuroscience research and drug development to provide insights into the dynamic relationship between vascular dysfunction and AD pathogenesis.

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Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction

Abstract

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