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Amyloid-Related Imaging Abnormalities in an Aged Squirrel Monkey with Cerebral Amyloid Angiopathy.
Heuer, Eric; Jacobs, Jessica; Du, Rebecca; Wang, Silun; Keifer, Orion P; Cintron, Amarallys F; Dooyema, Jeromy; Meng, Yuguang; Zhang, Xiaodong; Walker, Lary C.
Afiliación
  • Heuer E; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Jacobs J; Department of Psychology, University of Hawaii at Hilo, Hilo, HI, USA.
  • Du R; Department of Psychology, University of Hawaii at Hilo, Hilo, HI, USA.
  • Wang S; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Keifer OP; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Cintron AF; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Dooyema J; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Meng Y; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Zhang X; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Walker LC; Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
J Alzheimers Dis ; 57(2): 519-530, 2017.
Article en En | MEDLINE | ID: mdl-28269776
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-ß (Aß)-type cerebral amyloid angiopathy, an accumulation of misfolded Aß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Péptidos beta-Amiloides / Angiopatía Amiloide Cerebral Límite: Animals Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Péptidos beta-Amiloides / Angiopatía Amiloide Cerebral Límite: Animals Idioma: En Revista: J Alzheimers Dis Asunto de la revista: GERIATRIA / NEUROLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos