title: Early cerebrovascular inflammation in a transgenic mouse model of Alzheimer's disease.
abstract: Amyloid plaques associated with Alzheimer's disease (AD) induce inflammatory responses associated with activated microglia and reactive astrocytes, which exacerbate neurodegeneration through release of inflammatory cytokines, reactive oxygen species, and other factors. Inflammation contributes to neurodegeneration at later stages of AD, but it may also play a role in early disease pathogenesis. We found that before plaque deposition, amyloid precursor protein (APP)/presenilin 1 (PSEN1) transgenic mice (PSAPP mice), a well-characterized model of AD, exhibit evidence of cerebrovascular inflammation. Expression of the endothelial cell-specific antigen MECA-32 (mouse endothelial cell antigen-32) was upregulated in the cerebrovasculature of young PSAPP mice (3 months old) and was similar to that observed in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis characterized by neuroinflammation. MECA-32 is normally expressed in central and peripheral vasculature throughout development, but expression in the cerebrovasculature is downregulated on establishment of the blood-brain barrier (BBB). However, CNS inflammation triggers re-expression of MECA-32 in compromised cerebrovasculature. Our study indicates that MECA-32 may be a robust marker of cerebrovascular inflammation and compromised BBB integrity, triggered by soluble amyloid-β early in disease pathogenesis.
authors.affiliation: Discovery Neuroscience, Wyeth Research, Princeton, NJ, USA.
authors.forename: Dongzi
authors.initials: D
authors.lastname: Yu
authors.forename: Brian
authors.initials: B
authors.lastname: Corbett
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Reinhart
authors.forename: Seongeun J
authors.initials: SJ
authors.lastname: Cho
authors.forename: Jeannie
authors.initials: J
authors.lastname: Chin
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology; D020293:Vasculitis, Central Nervous System / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D000954:Antigens, Surface; C095910:MECA-32 antigen, mouse; C508853:PSEN1 protein, human; D053764:Presenilin-1