Different microvascular alterations underlie microbleeds and microinfarcts

Susanne J. van Veluw*, Ashley A. Scherlek, Whitney M. Freeze, Annemieke ter Telgte, Andre J. van der Kouwe, Brian J. Bacskai, Matthew P. Frosch, Steven M. Greenberg

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Web of Science)

Abstract

Objective Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid beta (A beta) in the walls of cortical vessels and the accrual of microbleeds and microinfarcts over time. The relationship between CAA severity and microbleeds and microinfarcts as well as the sequence of events that lead to lesion formation remain poorly understood. Methods We scanned intact formalin-fixed hemispheres of 12 CAA cases with magnetic resonance imaging (MRI), followed by histopathological examination in predefined areas and serial sectioning in targeted areas with multiple lesions. Results In total, 1,168 cortical microbleeds and 472 cortical microinfarcts were observed on ex vivo MRI. Increasing CAA severity at the whole-brain or regional level was not associated with the number of microbleeds or microinfarcts. However, locally, the density of A beta-positive cortical vessels was lower surrounding a microbleed compared to a simulated control lesion, and higher surrounding microinfarcts. Serial sectioning revealed that for (n = 28) microbleeds, both A beta (4%) and smooth muscle cells (4%) were almost never present in the vessel wall at the site of bleeding, but A beta was frequently observed upstream or downstream (71%), as was extensive fibrin(ogen) buildup (87%). In contrast, for (n = 22) microinfarcts, vascular A beta was almost always observed at the core of the lesion (91%, p <0.001) as well as upstream or downstream (82%), but few vessels associated with microinfarcts had intact smooth muscle cells (9%). Interpretation These observations provide a model for how a single neuropathologic process such as CAA may result in hemorrhagic or ischemic brain lesions potentially through 2 different mechanistic pathways. ANN NEUROL 2019;86:279-292

Original languageEnglish
Pages (from-to)279-292
Number of pages14
JournalAnnals of Neurology
Volume86
Issue number2
DOIs
Publication statusPublished - Aug 2019

Keywords

  • CEREBRAL AMYLOID ANGIOPATHY
  • CORTICAL MICROINFARCTS
  • BURDEN
  • SITES

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