J Stroke.  2015 Jan;17(1):17-30. 10.5853/jos.2015.17.1.17.

Cerebral Amyloid Angiopathy: Emerging Concepts

• Yamada M

• KMID: 2223683
• DOI: http://doi.org/10.5853/jos.2015.17.1.17

Abstract

Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid beta-protein (Abeta)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Abeta 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 Abeta40 for CAA and anti-Abeta 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 Abeta 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.

Keyword

Cerebral amyloid angiopathy; Amyloid beta-protein; Cerebrovascular disorders; MRI; PET; Cerebrospinal fluid

MeSH Terms

Alzheimer Disease
Amyloid
Amyloid beta-Peptides
Biomarkers
Biopsy
Blood Vessels
Brain
Cerebral Amyloid Angiopathy*
Cerebrospinal Fluid
Cerebrovascular Disorders
Dementia
Diagnosis
Epidemiology
Humans
Immunotherapy
Infarction
Inflammation
Leukoencephalopathies
Ligands
Magnetic Resonance Imaging
Neuroimaging
Pathology
Plaque, Amyloid
Positron-Emission Tomography
Risk Factors
Siderosis
Stroke
Subarachnoid Hemorrhage
Amyloid
Amyloid beta-Peptides
Ligands