Teresa Mescher1, Philip J Boyer2, Andrew N Bubak3, James E Hassell4, Maria A Nagel5. 1. Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, United States. Electronic address: teresa.mescher@cuanschutz.edu. 2. Department of Pathology, East Carolina University Brody School of Medicine, Greenville, NC 27934, United States. Electronic address: boyerp14@ecu.edu. 3. Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, United States. Electronic address: andrew.bubak@cuanschutz.edu. 4. Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, United States. Electronic address: james.hasselljr@cuanschutz.edu. 5. Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, United States; Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO 80045, United States. Electronic address: maria.nagel@cuanschutz.edu.
Abstract
OBJECTIVE: Varicella zoster virus (VZV) vasculopathy and cerebral amyloid angiopathy (CAA) have similar clinical presentations: both affect cerebrovasculature in the elderly, produce hemorrhage, and can have a protracted course of cognitive decline and other neurological deficits. The cause of CAA is unknown, but amyloid-beta (Aβ) is found within arterial walls. Recent studies show that VZV induces Aβ and amylin expression and an amyloid-promoting environment. Thus, we determined if VZV was present in CAA-affected arteries. METHODS: Two subjects with pathologically-verified CAA were identified postmortem and frontal lobes analyzed by immunohistochemistry for arteries containing VZV, Aβ, and amylin and H&E for pathological changes. VZV antigen detection was confirmed by PCR for VZV DNA in the same region. RESULTS: In both CAA cases, sections with cerebral arteries containing VZV antigen with corresponding VZV DNA were identified; VZV antigen co-localized with Aβ in media of arteries with histological changes characteristic of CAA. Amylin was also seen in the intima of a VZV-positive artery in the diabetic subject. Not all Aβ-containing arteries had VZV, but all VZV-positive arteries contained Aβ. CONCLUSIONS: VZV antigen co-localized with Aβ in some affected arteries from two CAA cases, suggesting a possible association between VZV infection and CAA.
OBJECTIVE: Varicella zoster virus (VZV) vasculopathy and cerebral amyloid angiopathy (CAA) have similar clinical presentations: both affect cerebrovasculature in the elderly, produce hemorrhage, and can have a protracted course of cognitive decline and other neurological deficits. The cause of CAA is unknown, but amyloid-beta (Aβ) is found within arterial walls. Recent studies show that VZV induces Aβ and amylin expression and an amyloid-promoting environment. Thus, we determined if VZV was present in CAA-affected arteries. METHODS: Two subjects with pathologically-verified CAA were identified postmortem and frontal lobes analyzed by immunohistochemistry for arteries containing VZV, Aβ, and amylin and H&E for pathological changes. VZV antigen detection was confirmed by PCR for VZV DNA in the same region. RESULTS: In both CAA cases, sections with cerebral arteries containing VZV antigen with corresponding VZV DNA were identified; VZV antigen co-localized with Aβ in media of arteries with histological changes characteristic of CAA. Amylin was also seen in the intima of a VZV-positive artery in the diabetic subject. Not all Aβ-containing arteries had VZV, but all VZV-positive arteries contained Aβ. CONCLUSIONS: VZV antigen co-localized with Aβ in some affected arteries from two CAA cases, suggesting a possible association between VZV infection and CAA.
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Authors: Andrew N Bubak; Christina N Como; James E Hassell; Teresa Mescher; Seth E Frietze; Christy S Niemeyer; Randall J Cohrs; Maria A Nagel Journal: Neurol Neuroimmunol Neuroinflamm Date: 2021-11-10