title: Abeta species removal after abeta42 immunization.
abstract: Neuropathologic examination of 3 patients with Alzheimer disease in the Elan Pharmaceuticals trial using antibodies specific for different Abeta species showed in one case, 4 months after the immunization, evidence of a stage of active plaque clearance with "moth-eaten" plaques and abundant Abeta phagocytosis by microglia. At 1 to 2 years after immunization, 2 cases showed extensive areas cleared of plaques (69% and 86% of the temporal cortex was plaque-free). Cortex cleared of plaques in all 3 cases had a characteristic constellation of features, including a very low plaque burden, sparse residual dense plaque cores, and phagocytosed Abeta within microglia. There was resolution of tau-containing dystrophic neurites, although other features of tau pathology (tangles and neuropil threads) remained and cerebral amyloid angiopathy persisted. Although most antibodies generated by Abeta42 immunization in humans bind the intact N-terminus, immunohistochemistry with specific antibodies showed clearance of all major species of Abeta (Abeta40, Abeta42, and N-terminus truncated Abeta). Abeta immunotherapy can clear all Abeta species from the cortex. However, if it is to be used for treatment of established Alzheimer disease, then the residual tau pathology and cerebral amyloid angiopathy require further study.
authors.affiliation: Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK.
authors.forename: James A R
authors.initials: JA
authors.lastname: Nicoll
authors.forename: Edward
authors.initials: E
authors.lastname: Barton
authors.forename: Delphine
authors.initials: D
authors.lastname: Boche
authors.forename: Jim W
authors.initials: JW
authors.lastname: Neal
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Petrina
authors.initials: P
authors.lastname: Thompson
authors.forename: Christina
authors.initials: C
authors.lastname: Vlachouli
authors.forename: David
authors.initials: D
authors.lastname: Wilkinson
authors.forename: Antony
authors.initials: A
authors.lastname: Bayer
authors.forename: Dora
authors.initials: D
authors.lastname: Games
authors.forename: Peter
authors.initials: P
authors.lastname: Seubert
authors.forename: Dale
authors.initials: D
authors.lastname: Schenk
authors.forename: Clive
authors.initials: C
authors.lastname: Holmes
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D023582:Alzheimer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D017628:Microglia / Q000473:pathology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000473:pathology; D019600:Neuropil Threads / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D010587:Phagocytosis; D016032:Randomized Controlled Trials as Topic
chemical_list: D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments