Apolipoprotein E and clusterin inhibit the early phase of amyloid-β aggregation in an in vitro model of cerebral amyloid angiopathy

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

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Evidence of amyloid-β cerebral amyloid angiopathy transmission through neurosurgery

Acta Neuropathologica ◽

10.1007/s00401-018-1822-2 ◽

2018 ◽

Vol 135 (5) ◽

pp. 671-679 ◽

Cited By ~ 38

Author(s):

Zane Jaunmuktane ◽

Annelies Quaegebeur ◽

Ricardo Taipa ◽

Miguel Viana-Baptista ◽

Raquel Barbosa ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Amyloid Β ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Vessels Sing Their ARIAs: The Role of Vascular Amyloid in the Age of Aducanumab

Stroke ◽

10.1161/strokeaha.121.036873 ◽

2021 ◽

Author(s):

Lukas Sveikata ◽

Andreas Charidimou ◽

Anand Viswanathan

Keyword(s):

Clinical Trials ◽

Alzheimer Disease ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Β ◽

High Rate ◽

Amyloid Angiopathy ◽

Cerebrovascular Pathology ◽

Cerebral Amyloid

We review the implications of the recently approved aducanumab amyloid-β immunotherapy for treating Alzheimer disease with comorbid cerebral amyloid angiopathy. In clinical trials, amyloid-β immunotherapy has been associated with a high rate of amyloid-related imaging abnormalities, potentially driven by coexisting cerebral amyloid angiopathy. Therefore, immunotherapy’s efficacy in patients may be modified by coexisting cerebrovascular pathology. We discuss the contributions of cerebral amyloid angiopathy on the development of amyloid-related imaging abnormalities and propose strategies to identify cerebral amyloid angiopathy in patients considered for immunotherapy.

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Understanding the Pathophysiology of Cerebral Amyloid Angiopathy

International Journal of Molecular Sciences ◽

10.3390/ijms21103435 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3435

Author(s):

Laura Gatti ◽

Francesca Tinelli ◽

Emma Scelzo ◽

Francesco Arioli ◽

Giuseppe Di Fede ◽

...

Keyword(s):

Animal Models ◽

Cerebral Amyloid Angiopathy ◽

Small Vessel Disease ◽

Amyloid Angiopathy ◽

Continuous Increase ◽

Disease Biomarkers ◽

Cerebral Amyloid ◽

Disease Stages ◽

Spontaneous Intracerebral Haemorrhage

Cerebral amyloid angiopathy (CAA), one of the main types of cerebral small vessel disease, is a major cause of spontaneous intracerebral haemorrhage and an important contributor to cognitive decline in elderly patients. Despite the number of experimental in vitro studies and animal models, the pathophysiology of CAA is still largely unknown. Although several pathogenic mechanisms including an unbalance between production and clearance of amyloid beta (Aβ) protein as well as ‘the prion hypothesis’ have been invoked as possible disease triggers, they do not explain completely the disease pathogenesis. This incomplete disease knowledge limits the implementation of treatments able to prevent or halt the clinical progression. The continuous increase of CAA patients makes imperative the development of suitable experimental in vitro or animal models to identify disease biomarkers and new pharmacological treatments that could be administered in the early disease stages to prevent irreversible changes and disease progression.

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