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

被引：89

作者：

Perosa, Valentina ^{[1
,2
,3
]}

Oltmer, Jan ^{[4
,5
]}

Munting, Leon P. ^{[6
,7
]}

Freeze, Whitney M. ^{[7
,8
]}

Auger, Corinne A. ^{[6
]}

Scherlek, Ashley A. ^{[6
,9
]}

van der Kouwe, Andre J. ^{[4
,5
]}

Iglesias, Juan Eugenio ^{[4
,5
,10
,11
]}

Atzeni, Alessia ^{[10
]}

Bacskai, Brian J. ^{[6
]}

Viswanathan, Anand ^{[1
]}

Frosch, Matthew P. ^{[6
,12
]}

Greenberg, Steven M. ^{[1
]}

van Veluw, Susanne J. ^{[1
,6
,7
]}

机构：

[1] Harvard Med Sch, Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, Cambridge Str 175,Suite 300, Boston, MA 02114 USA

[2] Otto Von Guericke Univ, Dept Neurol, Magdeburg, Germany

[3] German Ctr Neurodegenerat Dis DZNE, Magdeburg, Germany

[4] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA

[5] Harvard Med Sch, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA

[6] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA

[7] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands

[8] Maastricht Univ, Dept Neuropsychol & Psychiat, Maastricht, Netherlands

[9] Rush Univ, Med Ctr, Rush Alzheimer Dis Ctr, Chicago, IL 60612 USA

[10] UCL, Ctr Med Image Comp, London, England

[11] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[12] Harvard Med Sch, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Neuropathol Serv, Boston, MA 02115 USA

来源：

ACTA NEUROPATHOLOGICA | 2022年 / 143卷 / 03期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

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;

D O I：

10.1007/s00401-021-02393-1

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：331 / 348

页数：18

共 75 条

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