title: Amyloid-Related Imaging Abnormalities in an Aged Squirrel Monkey with Cerebral Amyloid Angiopathy.
abstract: Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer's disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* susceptibility weighted images. ARIA in general has been linked to the presence of amyloid-β (Aβ)-type cerebral amyloid angiopathy, an accumulation of misfolded Aβ protein in the vascular wall that impairs the integrity of brain blood vessels. However, the pathobiology of ARIA remains poorly understood, in part due to the absence of an animal model of the disorder that would enable a contemporaneous analysis of tissue integrity in the affected region. Here we describe both ARIA-E and ARIA-H in an aged squirrel monkey (Saimiri sciureus), a nonhuman primate model of naturally occurring cerebral amyloid angiopathy. Histopathologic examination of the anomalous region revealed reactive astrocytosis and microgliosis, infiltration of systemic inflammatory/immune cells, damage to axons and myelin, and hemosiderin deposition. The disruption of axons in particular suggests that ARIA-E could have functional consequences for affected regions. The squirrel monkey model can be useful for studying the pathogenesis and long-term effects of ARIA, and for testing the safety and efficacy of emerging therapies for Alzheimer's disease.
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.|Department of Psychology, University of Hawaii at Hilo, Hilo, HI, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Heuer
authors.affiliation: Department of Psychology, University of Hawaii at Hilo, Hilo, HI, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Jacobs
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Du
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Silun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Orion P
authors.initials: OP
authors.lastname: Keifer
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Amarallys F
authors.initials: AF
authors.lastname: Cintron
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Jeromy
authors.initials: J
authors.lastname: Dooyema
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.|Department of Neurology, and Alzheimer's Disease Research Center, Emory University, Atlanta, GA, USA.
authors.forename: Lary C
authors.initials: LC
authors.lastname: Walker
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D012453:Saimiri
chemical_list: D016229:Amyloid beta-Peptides
keywords: ARIA-E; ARIA-H; Alzheimer’s disease; amyloid-beta; amyloid-related imaging abnormalities; immunotherapy; inflammation; magnetic resonance imaging; vascular disease