Cortical superficial siderosis is associated with reactive astrogliosis in cerebral amyloid angiopathy

Corinne A Auger; Valentina Perosa; Steven M Greenberg; Susanne J van Veluw; Mariel G Kozberg

doi:10.1186/s12974-023-02872-0

Cortical superficial siderosis is associated with reactive astrogliosis in cerebral amyloid angiopathy

J Neuroinflammation. 2023 Aug 27;20(1):195. doi: 10.1186/s12974-023-02872-0.

Authors

Corinne A Auger¹, Valentina Perosa², Steven M Greenberg², Susanne J van Veluw^{1

2}, Mariel G Kozberg^{3

4}

Affiliations

¹ MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Boston, MA, 02129, USA.
² J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge Street, Boston, MA, 02114, USA.
³ MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114, 16th Street, Boston, MA, 02129, USA. mkozberg@mgh.harvard.edu.
⁴ J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge Street, Boston, MA, 02114, USA. mkozberg@mgh.harvard.edu.

Abstract

Background: Cortical superficial siderosis (cSS) has recently emerged as one of the most important predictors of symptomatic intracerebral hemorrhage and is a risk factor for post-stroke dementia in cerebral amyloid angiopathy (CAA). However, it remains unknown whether cSS is just a marker of severe CAA pathology or may itself contribute to intracerebral hemorrhage risk and cognitive decline. cSS is a chronic manifestation of convexal subarachnoid hemorrhage and is neuropathologically characterized by iron deposits in the superficial cortical layers. We hypothesized that these iron deposits lead to local neuroinflammation, a potentially contributory pathway towards secondary tissue injury.

Methods: Accordingly, we assessed the distribution of inflammatory markers in relation to cortical iron deposits in post-mortem tissue from CAA cases. Serial sections from the frontal, parietal, temporal, and occipital lobes of nineteen autopsy cases with CAA were stained with Perls' Prussian blue (iron) and underwent immunohistochemistry against glial fibrillary acidic protein (GFAP, reactive astrocytes) and cluster of differentiation 68 (CD68, activated microglia/macrophages). Digitized sections were uploaded to the cloud-based Aiforia^® platform, where deep-learning algorithms were utilized to detect tissue, iron deposits, and GFAP-positive and CD68-positive cells.

Results: We observed a strong local relationship between cortical iron deposits and reactive astrocytes. Like cSS-related iron, reactive astrocytes were mainly found in the most superficial layers of the cortex. Although we observed iron within both astrocytes and activated microglia/macrophages on co-stains, there was no clear local relationship between the density of microglia/macrophages and the density of iron deposits.

Conclusion: Iron deposition resulting from cSS is associated with local reactive astrogliosis.

Keywords: Astrogliosis; Cerebral amyloid angiopathy; Cortical superficial siderosis; Neuroinflammation; Reactive astrocytes.

MeSH terms

Cerebral Amyloid Angiopathy* / complications
Cerebral Hemorrhage
Gliosis
Humans
Inflammation
Iron
Siderosis* / complications

Substances

Iron

Abstract

MeSH terms

Substances

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