Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease.
Inflammation, insoluble protein deposition and neuronal cell loss are important features of the Alzheimer's disease (AD) brain. S100B is associated with the neuropathological hallmarks of AD where it is thought to play a role in neuritic pathology. S100A8, S100A9 and S100A12 comprise a new group of inflammation-associated proteins that are constitutively expressed by neutrophils and inducible in numerous inflammatory cells. We investigated expression of S100B, S100A8, S100A9 and S100A12 in brain samples from sporadic and familial (PS-1) AD cases and controls using immunohistochemistry and Western blot analysis. S100B, S100A9 and S100A12, but not S100A8, were consistently associated with the neuropathological hallmarks of AD. Western blot analysis confirmed significant increases in soluble S100A9 in PS-1 AD compared to controls. S100A9 complexes that were resistant to reduction were also evident in brain extracts. A reactive component of a size consistent with hexameric S100A12 was seen in all cases. This study indicates a potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in AD.
Shepherd
C E
CE
Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney 2031, Australia. C.Shepherd@unsw.edu.au
Goyette
J
J
Utter
V
V
Rahimi
F
F
Yang
Z
Z
Geczy
C L
CL
Halliday
G M
GM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001923:Brain Chemistry; D040502:Calgranulin B / Q000032:analysis*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry; D009418:S100 Proteins / Q000032:analysis*; D000067616:S100A12 Protein
D040502:Calgranulin B; D018836:Inflammation Mediators; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human