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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

Immunohistochemistry of adjacent brain sections with antibodies to Aβ40 (A) and Aβ42 (B). Positive immunoreactivity to Aβ40 is mainly observed in vessel walls (CAA) (A), whereas Aβ42 immunoreactivity is mainly observed in the brain parenchyma (senile plaques) (B).
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Figure 2: Immunohistochemistry of adjacent brain sections with antibodies to Aβ40 (A) and Aβ42 (B). Positive immunoreactivity to Aβ40 is mainly observed in vessel walls (CAA) (A), whereas Aβ42 immunoreactivity is mainly observed in the brain parenchyma (senile plaques) (B).

Mentions: Aβ is cleaved from the β-amyloid precursor protein (AβPP) by β-secretase and γ-secretase. Heterogeneity of the C-terminal is present, and the length of Aβ in senile plaques is mainly 42-43 residues (Aβ42), while that of cerebrovascular Aβ (CAA) is mainly 39-40 residues (Aβ40) (Figure 2).15,16 Recent studies suggest that Aβ in CAA is derived from the brain [see review5]; after release from neurons, Aβ42 easily aggregates and deposits in the brain parenchyma as senile plaques; whereas, Aβ40 does not aggregate as easily as Aβ42, and is transported, through periarterial interstitial fluid drainage pathways, to blood vessels for clearance. In this process, Aβ40 aggregates on vascular basement membranes, as first proposed by Weller.17


Cerebral amyloid angiopathy: emerging concepts.

Yamada M - J Stroke (2015)

Immunohistochemistry of adjacent brain sections with antibodies to Aβ40 (A) and Aβ42 (B). Positive immunoreactivity to Aβ40 is mainly observed in vessel walls (CAA) (A), whereas Aβ42 immunoreactivity is mainly observed in the brain parenchyma (senile plaques) (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Immunohistochemistry of adjacent brain sections with antibodies to Aβ40 (A) and Aβ42 (B). Positive immunoreactivity to Aβ40 is mainly observed in vessel walls (CAA) (A), whereas Aβ42 immunoreactivity is mainly observed in the brain parenchyma (senile plaques) (B).
Mentions: Aβ is cleaved from the β-amyloid precursor protein (AβPP) by β-secretase and γ-secretase. Heterogeneity of the C-terminal is present, and the length of Aβ in senile plaques is mainly 42-43 residues (Aβ42), while that of cerebrovascular Aβ (CAA) is mainly 39-40 residues (Aβ40) (Figure 2).15,16 Recent studies suggest that Aβ in CAA is derived from the brain [see review5]; after release from neurons, Aβ42 easily aggregates and deposits in the brain parenchyma as senile plaques; whereas, Aβ40 does not aggregate as easily as Aβ42, and is transported, through periarterial interstitial fluid drainage pathways, to blood vessels for clearance. In this process, Aβ40 aggregates on vascular basement membranes, as first proposed by Weller.17

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