Basal lamina changes in neurodegenerative disorders

Abstract

Background: Neurodegenerative disorders are a group of age-associated diseases characterized by progressive degeneration of the structure and function of the CNS. Two key pathological features of these disorders are blood-brain barrier (BBB) breakdown and protein aggregation.

Main body: The BBB is composed of various cell types and a non-cellular component---the basal lamina (BL). Although how different cells affect the BBB is well studied, the roles of the BL in BBB maintenance and function remain largely unknown. In addition, located in the perivascular space, the BL is also speculated to regulate protein clearance via the meningeal lymphatic/glymphatic system. Recent studies from our laboratory and others have shown that the BL actively regulates BBB integrity and meningeal lymphatic/glymphatic function in both physiological and pathological conditions, suggesting that it may play an important role in the pathogenesis and/or progression of neurodegenerative disorders. In this review, we focus on changes of the BL and its major components during aging and in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). First, we introduce the vascular and lymphatic systems in the CNS. Next, we discuss the BL and its major components under homeostatic conditions, and summarize their changes during aging and in AD, PD, and ALS in both rodents and humans. The functional significance of these alterations and potential therapeutic targets are also reviewed. Finally, key challenges in the field and future directions are discussed.

Conclusions: Understanding BL changes and the functional significance of these changes in neurodegenerative disorders will fill the gap of knowledge in the field. Our goal is to provide a clear and concise review of the complex relationship between the BL and neurodegenerative disorders to stimulate new hypotheses and further research in this field.

Keywords: Basal lamina; Blood-Brain Barrier; Laminin; Neurodegenerative disorders; Perlecan.

Fig. 1

Diagram illustration of the vasculature and BL layers in the CNS. a Scheme of the CNS blood vessels and meningeal lymphatic/glymphatic system. The inset highlights the cross-section view of a meningeal artery. b Scheme of various BL layers and cellular components at the arterial/arteriole, capillary, and post-capillary venule levels in the CNS vasculature. BL: basal lamina; eBL: endothelial basal lamina; EC: endothelial cell; pBL: parenchymal basal lamina; PVM: perivascular macrophage; SMC: smooth muscle cell

Fig. 2

Structural illustration of major BL components collagen and laminin. a Collagen IV monomer, trimer, and its suprastructure. 7S, 7S domain; NC1, NC1 domain. b Laminin monomer and its suprastructure. α, β, and γ: laminin-α, -β, and -γ chains, respectively

Fig. 3

BL changes in aging and neurological disorders. Diagram illustrations showing changes of BL, endothelial cells, pericytes, microglia, neurons, and protein aggregates in aging and three neurodegenerative disorders (AD, PD, and ALS). BL: basal lamina; EC: endothelial cell; PC: pericytes; As: astrocytes; rM: resting microglia; pM: primed microglia; aM: activated microglia; hN: healthy neurons; iN: injured neurons; Aβ: β-amyloid; α-Syn: α-synuclein; SC: serum components; AD: Alzheimer’s disease; PD: Parkinson’s disease; ALS: amyotrophic lateral sclerosis