Detection of Spontaneously Occuring Amyloid Plaques in a Primate Model of Alzheimer's Disease

INTRODUCTION: Alzheimer’s disease (AD) is the most common type of neurodegenerative diseases. Amyloid deposits/plaques, one of its characteristic lesions, constitute the main target for diagnostics and therapeutics and have previously been identified in transgenic mouse models of AD using magnetic resonance (MR) microscopy [1,2]. These plaques typically appear as hypointense spots on T2 or T2*-weighted MR images and their sizes range from 50 μm to 200 μm. Plaques from humans are however very different than those of rodents. For example they are less compact and their detection is expected to be much more difficult than those of rodents. As a first step toward imaging amyloid plaques in humans, we evaluated plaques detection in a Primate model (the mouse lemur (Microcebus murinus)) developing spontaneously amyloid plaques [3]. Adult animals weight approximately 100 g and have a brain that measures approximately 23 mm, with a maximum width of 18 mm. These characteristics, added to their phylogenic proximity with humans, make them a promising model to evaluate protocols to detect amyloid plaques in humans. To detect amyloid plaques in mice, some investigators have used targeted contrast agents that selectively bind to amyloid plaques [4]. Such agents are not readily available and cannot yet be clinically used. Various studies demonstrated that a non-targeted contrast agent such as Gadolinium-DOTA (Gd or passive staining protocols) coupled with a very high resolution allows to identify ex-vivo but also in–vivo amyloid deposits in the brains of the transgenic mice [5,6]. Here we demonstrate that this method allows to detect spontaneously occurring amyloid plaques in the brain of aged primates.