Exp Neurobiol.
2023 Aug;32(4):216-246. 10.5607/en23014.
Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases
- Affiliations
-
- 1Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
- 2Department of Neurology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
- 3Department of Brain Science, Ajou University School of Medicine, Suwon 16499, Korea
- KMID: 2546571
- DOI: http://doi.org/10.5607/en23014
Abstract
- This review examines the role of impaired amyloid-β clearance in the accumulation of amyloid-β in the brain and the periphery, which is closely associated with Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The molecular mechanism underlying amyloid-β accumulation is largely unknown, but recent evidence suggests that impaired amyloid-β clearance plays a critical role in its accumulation. The review provides an overview of recent research and proposes strategies for efficient amyloid-β clearance in both the brain and periphery. The clearance of amyloid-β can occur through enzymatic or non-enzymatic pathways in the brain, including neuronal and glial cells, blood-brain barrier, interstitial fluid bulk flow, perivascular drainage, and cerebrospinal fluid absorption-mediated pathways. In the periphery, various mechanisms, including peripheral organs, immunomodulation/immune cells, enzymes, amyloid-β-binding proteins, and amyloid-β-binding cells, are involved in amyloid-β clearance. Although recent findings have shed light on amyloid-β clearance in both regions, opportunities remain in areas where limited data is available. Therefore, future strategies that enhance amyloid-β clearance in the brain and/or periphery, either through central or peripheral clearance approaches or in combination, are highly encouraged. These strategies will provide new insight into the disease pathogenesis at the molecular level and explore new targets for inhibiting amyloid-β deposition, which is central to the pathogenesis of sporadic AD (amyloid-β in parenchyma) and CAA (amyloid-β in blood vessels).
