Perivascular space dilation is associated with vascular amyloid-β accumulation in the overlying cortex

V. Perosa*, J. Oltmer, L.P. Munting, W.M. Freeze, C.A. Auger, A.A. Scherlek, A.J. van der Kouwe, J.E. Iglesias, A. Atzeni, B.J. Bacskai, A. Viswanathan, M.P. Frosch, S.M. Greenberg, S.J. van Veluw

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-beta (A beta) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular A beta accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD.
Original languageEnglish
Pages (from-to)331-348
Number of pages18
JournalActa Neuropathologica
Volume143
Issue number3
Early online date20 Dec 2021
DOIs
Publication statusPublished - Mar 2022

Keywords

  • Cerebral amyloid angiopathy
  • Cerebral small vessel disease
  • Clearance
  • Ex vivo MRI
  • Enlarged perivascular spaces
  • VIRCHOW-ROBIN SPACES
  • SMALL-VESSEL DISEASE
  • WHITE-MATTER
  • ALZHEIMERS-DISEASE
  • GLYMPHATIC DYSFUNCTION
  • MRI MARKER
  • BRAIN
  • ANGIOPATHY
  • PATHOLOGY
  • PATHWAY

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