Oligomeric Pyroglutamate Amyloid-β is Present in Microglia and a Subfraction of Vessels in Patients with Alzheimer's Disease: Implications for Immunotherapy

Article type: Research Article

Authors: Wirths, Oliver^{a; *} | Hillmann, Antje^a | Pradier, Laurent^b | Härtig, Wolfgang^c | Bayer, Thomas A.^a

Affiliations: [a] Division of Molecular Psychiatry, Georg-August-University Goettingen, University Medicine Goettingen, Germany | [b] Sanofi-Aventis, Therapeutic Strategy Unit Aging, Chilly-Mazarin, France | [c] Faculty of Medicine, Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany

Correspondence: [*] Correspondence to: Oliver Wirths, Ph.D and Thomas A. Bayer, Ph.D, Division of Molecular Psychiatry, Georg-August-University Goettingen, University Medicine Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany. E-mails: owirths@gwdg.de; tbayer@gwdg.de (T.A. Bayer).. E-mails: owirths@gwdg.de; tbayer@gwdg.de (T.A. Bayer).

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.

Keywords: 9D5, Alzheimer's disease, amyloid, APP/PS1KI transgenic mouse model, gliosis, microglia, pyroglutamate Aβ, rhesus monkey

DOI: 10.3233/JAD-121945

Journal: Journal of Alzheimer's Disease, vol. 35, no. 4, pp. 741-749, 2013