title: Microglial alterations in human Alzheimer's disease following Aβ42 immunization.
abstract: OBJECTIVE
  In Alzheimer's disease (AD), microglial activation prompted by the presence of amyloid has been proposed as an important contributor to the neurodegenerative process. Conversely following Aβ immunization, phagocytic microglia have been implicated in plaque removal, potentially a beneficial effect. We have investigated the effects of Aβ42 immunization on microglial activation and the relationship with Aβ42 load in human AD.
  
  
  METHODS
  Immunostaining against Aβ42 and microglia (CD68 and HLA-DR) was performed in nine immunized AD cases (iAD - AN1792, Elan Pharmaceuticals) and eight unimmunized AD (cAD) cases.
  
  
  RESULTS
  Although the Aβ42 load (% area stained of total area examined) was lower in the iAD than the cAD cases (P=0.036), the CD68 load was higher (P=0.046). In addition, in the iAD group, the CD68 level correlated with the Aβ42 load, consistent with the immunization upregulating microglial phagocytosis when plaques are present. However, in two long-surviving iAD patients in whom plaques had been extensively cleared, the CD68 load was less than in controls. HLA-DR quantification did not show significant difference implying that the microglial activation may have related specifically to their phagocytic function. CD68 and HLA-DR loads in the pons were similar in both groups, suggesting that the differences in microglial activation in the cortex were due to the presence of AD pathology.
  
  
  CONCLUSIONS
  Our findings suggest that Aβ42 immunization modifies the function of microglia by increasing their phagocytic activity and when plaques have been cleared, the level of phagocytosis is decreased below that seen in unimmunized AD.
authors.affiliation: Division of Clinical Neurosciences, School of Medicine, University of Southampton, UK. e.zotova@soton.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Zotova
authors.forename: C
authors.initials: C
authors.lastname: Holmes
authors.forename: D
authors.initials: D
authors.lastname: Johnston
authors.forename: J W
authors.initials: JW
authors.lastname: Neal
authors.forename: J A R
authors.initials: JA
authors.lastname: Nicoll
authors.forename: D
authors.initials: D
authors.lastname: Boche
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000627:therapeutic use; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000473:pathology / Q000628:therapy; D000097382:CD68 Molecule
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C437846:AN-1792; C545487:APP protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule