Functions of the basal lamina and ApoE in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder marked by the deposition of amyloid-beta (Aβ) peptides within the walls of small- and medium-sized cerebral vessels, including arteries and capillaries but rarely veins. This vascular amyloid burden compromises vessel integrity, causes hemorrhages, and contributes to cognitive decline. Efficient Aβ clearance is critical for preventing its pathological accumulation. Thus, understanding the molecular players within the vascular microenvironment is essential. Laminin, a key glycoprotein of the vascular basal lamina (BL), is fundamental to maintaining structural stability of the vessels and regulating interactions among endothelial cells, pericytes, and the extracellular matrix. However, controversial findings exist on how laminin regulates Aβ aggregation and clearance, with both inhibitory and facilitative effects reported. Genetic variations in laminin subunits, their cell-specific expression pattern, and BL remodeling during CAA further complicate this relationship. This review synthesizes current knowledge on vascular Aβ deposition and elimination in CAA, with a particular focus on the critical roles of the BL/laminin and ApoE in shaping the perivascular microenvironment. First, we introduce Aβ processing relevant to CAA and the mechanisms of Aβ clearance in the CNS. Next, laminin-Aβ interactions and their functions in Aβ clearance are summarized. Thirdly, laminin changes and BL remodeling in CAA are discussed. Finally, we discuss the knowledge gap in the field and fundamental questions that need to be answered in future research. Defining the functions of the BL and ApoE within the pathological context of Aβ-rich vasculature may yield new insights into CAA pathogenesis and reveal therapeutic targets to limit vascular amyloid accumulation. Our goal is to provide a concise review on this matter in order to facilitate new hypotheses in the field.