Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Longitudinal noninvasive magnetic resonance imaging of brain microhemorrhages in BACE inhibitor-treated APP transgenic mice

Beckmann, Nicolau and Doelemeyer, Arno and Zurbruegg, Stefan and Bigot, Karine and Theil, Diethilde and Frieauff, Wilfried and Kolly, Carine and Neddermann, Daniel and Kreutzer, Robert and Perrot, Ludovic and Brzak, Irena and Jacobson, Laura and Staufenbiel, Matthias and Neumann, Ulf and Shimshek, Derya (2016) Longitudinal noninvasive magnetic resonance imaging of brain microhemorrhages in BACE inhibitor-treated APP transgenic mice. Neurobiology of Aging, 45. pp. 50-60. ISSN 01974580

Abstract

Currently, several immunotherapy- and BACE inhibitor-based approaches are being tested in the clinic for the treatment of Alzheimer`s disease. A crucial mechanistically related safety concern in case of a fast removal of brain blood vessel-associated amyloid-beta is the exacerbation of microhemorrhages which is already present in the majority of Alzheimer patients. To investigate potential safety liabilities for long-term Bace inhibitor therapies we used aged APP23 mice, an Alzheimer disease model, which robustly develops cerebral amyloid angiopathy (CAA). MRI, a translational tool easily applied in clinical studies, was used for the detection of the very sparse events of microhemorrhages throughout the entire brain, with a subsequent histological validation. 3D reconstruction of in vivo MRI and serial Perls` stained sections allowed a one-to-one matching of lesions and their histopathological characterization. MRI detected small Perls`s positive areas with sufficient extent along the z-axis. Our data demonstrates that volumetric assessment by non-invasive MRI is sensitive and specific to monitor cerebral microhemorrhages in vivo and that Bace inhibitor NB-360 in contrast to β1 antibody treatment of aged APP23 for three months did not exacerbate microhemorrhages.

Item Type: Article
Date Deposited: 15 Jun 2016 23:45
Last Modified: 15 Jun 2016 23:45
URI: https://oak.novartis.com/id/eprint/26300

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.