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Cerebral amyloid angiopathy: emerging concepts.

Yamada M - J Stroke (2015)

Bottom Line: Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies).Moreover, cSS is closely associated with transient focal neurological episodes (TFNE).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

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 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.

No MeSH data available.


Related in: MedlinePlus

CAA and CAA-associated vasculopathies. Massive amyloid deposition of amyloid fibrils with degeneration of smooth muscle cells in the media (A). Microaneurysmal dilatation (arrow) with fibrinoid necrosis (*) (B). Thickening of the intima (arrow) and double barreling of vascular walls (arrowheads) (C). (A, electron micrograph, bar=1 µm; B, Congo red, original magnification 110×; C, Congo red, original magnification 170×).
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Figure 1: CAA and CAA-associated vasculopathies. Massive amyloid deposition of amyloid fibrils with degeneration of smooth muscle cells in the media (A). Microaneurysmal dilatation (arrow) with fibrinoid necrosis (*) (B). Thickening of the intima (arrow) and double barreling of vascular walls (arrowheads) (C). (A, electron micrograph, bar=1 µm; B, Congo red, original magnification 110×; C, Congo red, original magnification 170×).

Mentions: Pathologically, CAA is observed mainly in the leptomeningeal and cortical vessels of the cerebral lobes and cerebellum. For the distribution of CAA, the occipital lobe is preferentially affected,6 whereas CAA is uncommon in the basal ganglia, thalamus, brainstem, and white matter. In mild CAA, a small proportion of the leptomeningeal and superficial cortical vessels are affected with amyloid deposition. In severe CAA, most small arteries and arterioles are affected with marked amyloid deposition. Medium-sized leptomeningeal arteries show amyloid deposition in the outer regions of the media to the adventitia. Vessel walls of the small arteries and arterioles are often totally replaced by amyloid deposits, except for the endothelial cells. Electron microscopically, amyloid fibrils are focally deposited within the outer basement membrane of the vessels during the initial stage of CAA.10 Later, a large amount of amyloid fibrils accumulate with degeneration of smooth muscle cells of the media (Figure 1A). Amyloid deposits in capillaries and, occasionally, in arterioles or small arteries appear to infiltrate the surrounding parenchymal tissue, and accompany dystrophic neurites forming plaque-like structures (drüsige Entartung1/angiopathie dyshorique2). Recently, CAA in capillaries has been referred to as "capillary CAA (CAA-Type 1)," to distinguish it from non-capillary CAA (CAA-Type 2).11 Severe CAA is associated with vasculopathies including duplication ("double-barrel" lumen), obliterative intimal changes, hyaline degeneration, microaneurysmal dilatation, and fibrinoid necrosis (Figure 1B, C).12,13,14 These CAA-associated vasculopathies are the pathological basis of CAA-related cerebrovascular disorders. In particular, fibrinoid necrosis is closely associated with CAA-related hemorrhage.12,13,14


Cerebral amyloid angiopathy: emerging concepts.

Yamada M - J Stroke (2015)

CAA and CAA-associated vasculopathies. Massive amyloid deposition of amyloid fibrils with degeneration of smooth muscle cells in the media (A). Microaneurysmal dilatation (arrow) with fibrinoid necrosis (*) (B). Thickening of the intima (arrow) and double barreling of vascular walls (arrowheads) (C). (A, electron micrograph, bar=1 µm; B, Congo red, original magnification 110×; C, Congo red, original magnification 170×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325636&req=5

Figure 1: CAA and CAA-associated vasculopathies. Massive amyloid deposition of amyloid fibrils with degeneration of smooth muscle cells in the media (A). Microaneurysmal dilatation (arrow) with fibrinoid necrosis (*) (B). Thickening of the intima (arrow) and double barreling of vascular walls (arrowheads) (C). (A, electron micrograph, bar=1 µm; B, Congo red, original magnification 110×; C, Congo red, original magnification 170×).
Mentions: Pathologically, CAA is observed mainly in the leptomeningeal and cortical vessels of the cerebral lobes and cerebellum. For the distribution of CAA, the occipital lobe is preferentially affected,6 whereas CAA is uncommon in the basal ganglia, thalamus, brainstem, and white matter. In mild CAA, a small proportion of the leptomeningeal and superficial cortical vessels are affected with amyloid deposition. In severe CAA, most small arteries and arterioles are affected with marked amyloid deposition. Medium-sized leptomeningeal arteries show amyloid deposition in the outer regions of the media to the adventitia. Vessel walls of the small arteries and arterioles are often totally replaced by amyloid deposits, except for the endothelial cells. Electron microscopically, amyloid fibrils are focally deposited within the outer basement membrane of the vessels during the initial stage of CAA.10 Later, a large amount of amyloid fibrils accumulate with degeneration of smooth muscle cells of the media (Figure 1A). Amyloid deposits in capillaries and, occasionally, in arterioles or small arteries appear to infiltrate the surrounding parenchymal tissue, and accompany dystrophic neurites forming plaque-like structures (drüsige Entartung1/angiopathie dyshorique2). Recently, CAA in capillaries has been referred to as "capillary CAA (CAA-Type 1)," to distinguish it from non-capillary CAA (CAA-Type 2).11 Severe CAA is associated with vasculopathies including duplication ("double-barrel" lumen), obliterative intimal changes, hyaline degeneration, microaneurysmal dilatation, and fibrinoid necrosis (Figure 1B, C).12,13,14 These CAA-associated vasculopathies are the pathological basis of CAA-related cerebrovascular disorders. In particular, fibrinoid necrosis is closely associated with CAA-related hemorrhage.12,13,14

Bottom Line: Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies).Moreover, cSS is closely associated with transient focal neurological episodes (TFNE).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

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 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.

No MeSH data available.


Related in: MedlinePlus