Monomeric and oligomeric amyloid-β cause distinct Alzheimer's disease pathophysiological characteristics in astrocytes in human glymphatics-on-chip models.

ABSTRACT: Alzheimer's disease (AD) is marked by the aggregation of extracellular amyloid-β (Aβ) and astrocyte dysfunction. For Aβ oligomers or aggregates to be formed, there must be Aβ monomers present; however, the roles of monomeric Aβ (mAβ) and oligomeric Aβ (oAβ) in astrocyte pathogenesis are poorly understood. We cultured astrocytes in a brain-mimicking three-dimensional (3D) extracellular matrix and revealed that both mAβ and oAβ caused astrocytic atrophy and hyper-reactivity, but showed distinct Ca²⁺ changes in astrocytes. This 3D culture evolved into a microfluidic glymphatics-on-chip model containing astrocytes and endothelial cells with the interstitial fluid (ISF). The glymphatics-on-chip model not only reproduced the astrocytic atrophy, hyper-reactivity, and Ca²⁺ ch

SUBMITTER: Yslas AR 

PROVIDER: S-EPMC11302770 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature