PLoS By Category | Recent PLoS Articles

Neurological Disorders - Neuroscience - Physiology

APP Knockout Mice Experience Acute Mortality as the Result of Ischemia
Published: Thursday, August 09, 2012
Author: Maya A. Koike et al.

by Maya A. Koike, Alexander J. Lin, Jonathan Pham, Elaine Nguyen, James J. Yeh, Rombod Rahimian, Bruce J. Tromberg, Bernard Choi, Kim N. Green, Frank M. LaFerla

The incidence of Alzheimer’s disease increases in people who have had an ischemic episode. Furthermore, APP expression is increased following ischemic or hypoxic conditions, as is the production of the Aß peptide. To address the question of why APP and Aß are increased in hypoxic and ischemic conditions we induced an ischemic episode in APP knockout mice (APP-/-) and BACE1 knockout mice (BACE-/-). We find that both APP-/- and BACE-/- mice have a dramatically increased risk of mortality as a result of cerebral ischemia. Furthermore, APP knockout mice have reduced cerebral blood flow in response to hypoxia, while wild-type mice maintain or increase cerebral blood flow to the same conditions. The transcription factor, serum response factor (SRF), and calcium-binding molecule, calsequestrin, both involved in vascular regulation, are significantly altered in the brains of APP-/- mice compared to wild type controls. These results show that APP regulates cerebral blood flow in response to hypoxia, and that it, and its cleavage fragments, are crucial for rapid adaptation to ischemic conditions.