title: Oligomeric pyroglutamate amyloid-β is present in microglia and a subfraction of vessels in patients with Alzheimer's disease: implications for immunotherapy.
abstract: N-terminally truncated pyroglutamate amyloid-β (Aβ) starting at position 3 (AβpE3) represents a major fraction of Aβ peptides in Alzheimer's disease (AD). Recently, we have identified low molecular weight AβpE3 oligomers, which can be detected by 9D5, a novel mouse monoclonal antibody. In the present study, we analyzed the immunohistochemical staining profile in the brain of patients with AD and in the APP/PS1KI mouse model, as well as in aged rhesus monkeys. 9D5-positive microglia and blood vessels were found in many AD cases, in the transgenic mouse model, and in an aged macaque. The presence of 9D5-immunoreactivity in microglia indicates that low molecular weight AβpE3 oligomers may be phagocytosed, since in the APP/PS1KI model, Aβ is exclusively produced in neurons due to neuronal expression of transgenic AβPP.
authors.affiliation: Division of Molecular Psychiatry, Georg-August-University Goettingen, University Medicine Goettingen, Germany. owirths@gwdg.de
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
authors.forename: Antje
authors.initials: A
authors.lastname: Hillmann
authors.forename: Laurent
authors.initials: L
authors.lastname: Pradier
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016612:Paraffin Embedding; D010587:Phagocytosis; D053764:Presenilin-1 / Q000235:genetics; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D011761:Pyrrolidonecarboxylic Acid