Dataset Information

Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.

ABSTRACT:

Objective

A significant cause of spontaneous hemorrhages in the elderly is cerebral amyloid angiopathy (CAA), which causes degeneration of cerebral vessels, but the mechanisms are unclear.

Methods

We isolated leptomeningeal vessels from rapidly autopsied brains (the average of postmortem intervals was 3.28 hours) from 9 patients with CAA and 10 age-matched controls, and used molecular, cell biology, and immunohistochemical approaches to examine ?-site APP-cleaving enzyme 1 (BACE1) protein expression and enzymatic activities as well as tight junction molecular components in small- and medium-sized arteries of the cerebral cortex and leptomeninges.

Results

We not only identified that the cerebral vessels, including leptomeningeal and cortical vessels, synthesize and express BACE1, but also found a significant elevation of both BACE1 protein levels and enzymatic activities in leptomeningeal vessels from patients with CAA. Moreover, overexpression of BACE1 in endothelial cells resulted in a significant reduction of occludin, a tight junction protein in blood vessels.

Conclusion

These findings suggest that in addition to neurons, cerebral vascular cells express functional BACE1. Moreover, elevated vascular BACE1 may contribute to deficiency of occludin in cerebral vessels, which ultimately has a critical role in pathogenesis of CAA and its related hemorrhage.

SUBMITTER: Cheng X

PROVIDER: S-EPMC4032211 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.

Cheng Xin X He Ping P Yao Hailan H Dong Qiang Q Li Rena R Shen Yong Y

Neurology 20140416 19

<h4>Objective</h4>A significant cause of spontaneous hemorrhages in the elderly is cerebral amyloid angiopathy (CAA), which causes degeneration of cerebral vessels, but the mechanisms are unclear.<h4>Methods</h4>We isolated leptomeningeal vessels from rapidly autopsied brains (the average of postmortem intervals was 3.28 hours) from 9 patients with CAA and 10 age-matched controls, and used molecular, cell biology, and immunohistochemical approaches to examine β-site APP-cleaving enzyme 1 (BACE1) ...[more]

PMID: 24739782

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Project description:Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2(*) imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis, treatment, risk factors, and future perspectives.

Dataset Information

Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.

Objective

Methods

Results

Conclusion

Publications

Occludin deficiency with BACE1 elevation in cerebral amyloid angiopathy.

Similar Datasets

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