title: Extracellular matrix modulator lysyl oxidase colocalizes with amyloid-beta pathology in Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis--Dutch type.
abstract: Accumulation of amyloid-beta (Aβ) in brain vessel walls and parenchyma, known as cerebral amyloid angiopathy (CAA) and senile plaques (SPs), respectively, plays a key role in Alzheimer's disease (AD) and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) pathogenesis. Although the mechanisms underlying CAA and SP formation remain largely unknown, evidence is mounting that local alterations of the extracellular matrix (ECM) in the brain vessel wall and/or parenchyma play an important role. Lysyl oxidase (LOX, E.C. 1.4.3.13) is an inducible amine oxidase that modulates the ECM by catalyzing the formation of molecular covalent cross-links in ECM proteins. The aim of this study is to investigate the association of LOX with CAA and with classic and diffuse SPs in both AD and HCHWA-D cases. We observed an association of LOX with Aβ in CAA and with Aβ in both classic and diffuse SPs in AD and HCHWA-D cases. In addition, LOX staining was observed in reactive astrocytes associated with these lesions. We conclude that the ECM modulating enzyme LOX is associated with the Aβ-related pathological hallmarks of both AD and HCHWA-D, and that our findings provide additional insights into the mechanisms underlying the formation of these lesions.
authors.affiliation: Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. m.wilhelmus@vumc.nl
authors.forename: Micha M M
authors.initials: MM
authors.lastname: Wilhelmus
authors.forename: John G J M
authors.initials: JG
authors.lastname: Bol
authors.forename: Sjoerd G
authors.initials: SG
authors.lastname: van Duinen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D028243:Cerebral Amyloid Angiopathy, Familial / Q000201:enzymology* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000201:enzymology* / Q000473:pathology; D008249:Protein-Lysine 6-Oxidase / Q000032:analysis*
chemical_list: D016229:Amyloid beta-Peptides; D016326:Extracellular Matrix Proteins; D008249:Protein-Lysine 6-Oxidase