Targeting lysyl-oxidase (LOX) may facilitate intramural periarterial drainage for the treatment of Alzheimer's disease

• Published in: Cerebral circulation - cognition and behavior Vol. 5; p. 100171
• Main Authors: Kelly, Louise, Sharp, Matthew Macgregor, Thomas, Isabelle, Brown, Christopher, Schrag, Matthew, Antunes, Lissa Ventura, Solopova, Elena, Martinez-Gonzalez, José, Rodríguez, Cristina, Carare, Roxana Octavia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2023; Elsevier
• Subjects: Alzheimer's disease; Amyloid beta; Basement membrane; Cerebral amyloid angiopathy; Dementia; Lysyl oxidase; Cerebral amyloid angiopathy; Amyloid beta; Lysyl oxidase; Alzheimer's disease; Basement membrane; Dementia
• ISSN: 2666-2450; 2666-2450
• DOI: 10.1016/j.cccb.2023.100171

•Altered basement membrane lysyl oxidase (LOX) expression is associated with disease.•LOX expression is increased in Alzheimer's disease.•Increased LOX expression may contribute to the aetiology of Alzheimer's disease.•An alteration in LOX expression may alter intramural periarterial drainage. Alzheimer's disease is the commonest form of dementia. It is likely that a lack of clearance of amyloid beta (Aβ) results in its accumulation in the parenchyma as Aβ oligomers and insoluble plaques, and within the walls of blood vessels as cerebral amyloid angiopathy (CAA). The drainage of Aβ along the basement membranes of blood vessels as intramural periarterial drainage (IPAD), could be improved if the driving force behind IPAD could be augmented, therefore reducing Aβ accumulation. There are alterations in the composition of the vascular basement membrane in Alzheimer's disease. Lysyl oxidase (LOX) is an enzyme involved in the remodelling of the extracellular matrix and its expression and function is altered in various disease states. The expression of LOX is increased in Alzheimer's disease, but it is unclear whether this is a contributory factor in the impairment of IPAD in Alzheimer's disease. The pharmacological inhibition of LOX may be a strategy to improve IPAD and reduce the accumulation of Aβ in the parenchyma and within the walls of blood vessels.