Dataset Information

Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy.

ABSTRACT: Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA). However, their effects on clinical features has not been evaluated well. The purpose of this study is to investigate the clinical implication of these markers in clinical-radiologically diagnosed CAA. A total of 372 patients with possible or probable CAA who met the modified Boston criteria were recruited in a memory clinic setting. Cortical thickness was measured using surface based methods. Presence of restricted multiple lobar CMBs were independently associated with cortical thinning across the entire cortical regions while presence of CSS was independently associated with cortical thinning primarily in the bilateral frontal region. Presence of restricted multiple lobar CMBs was associated with impairment in all cognitive domains such as attention, language, visuospatial, memory and frontal executive functions while presence of CSS was associated with attention and frontal dysfunction. The relationships of restricted multiple lobar CMBs or CSS with cognitive impairment were partially mediated by thinning in the corresponding cortical regions. Our findings suggested that restricted multiple lobar CMBs and CSS affect distinctive clinical features, providing new insights into potential mechanisms in CAA.

SUBMITTER: Jang YK

PROVIDER: S-EPMC5700189 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy.

Jang Young Kyoung YK Kim Hee Jin HJ Lee Jin San JS Kim Yeo Jin YJ Kim Ko Woon KW Kim Yeshin Y Jang Hyemin H Lee Juyoun J Lee Jong Min JM Kim Seung-Joo SJ Yu Kyung-Ho KH Charidimou Andreas A Werring David J DJ Kim Sung Tae ST Na Duk L DL Seo Sang Won SW

Scientific reports 20171122 1

Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA). However, their effects on clinical features has not been evaluated well. The purpose of this study is to investigate the clinical implication of these markers in clinical-radiologically diagnosed CAA. A total of 372 patients with possible or probable CAA who met the modified Boston criteria were recruited in a memory clinic setting. Cortical t ...[more]

PMID: 29167486

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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.

Project description:Alzheimer's disease (AD) is characterized by amyloid beta (A?) deposits as plaques in the parenchyma and in the walls of cortical and leptomeningeal blood vessels of the brain called cerebral amyloid angiopathy (CAA). It is suggested that CAA type-1, which refers to amyloid deposition in both capillaries and larger vessels, adds to the symptomatic manifestation of AD and correlates with disease severity. Currently, CAA cannot be diagnosed pre-mortem and disease mechanisms involved in CAA are elusive. To obtain insight in the disease mechanism of CAA and to identify marker proteins specifically associated with CAA we performed a laser dissection microscopy assisted mass spectrometry analysis of post-mortem human brain tissue of (I) AD cases with only amyloid deposits in the brain parenchyma and no vascular related amyloid, (II) AD cases with severe CAA type-1 and no or low numbers of parenchymal amyloid deposits and (III) cognitively healthy controls without amyloid deposits. By contrasting the quantitative proteomics data between the three groups, 29 potential CAA-selective proteins were identified. A selection of these proteins was analysed by immunoblotting and immunohistochemistry to confirm regulation and to determine protein localization and their relation to brain pathology. In addition, specificity of these markers in relation to other small vessel diseases including prion CAA, CADASIL, CARASAL and hypertension related small vessel disease was assessed using immunohistochemistry.Increased levels of clusterin (CLU), apolipoprotein E (APOE) and serum amyloid P-component (APCS) were observed in AD cases with CAA. In addition, we identified norrin (NDP) and collagen alpha-2(VI) (COL6A2) as highly selective markers that are clearly present in CAA yet virtually absent in relation to parenchymal amyloid plaque pathology. NDP showed the highest specificity to CAA when compared to other small vessel diseases. The specific changes in the proteome of CAA provide new insight in the pathogenesis and yields valuable selective biomarkers for the diagnosis of CAA.

Dataset Information

Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy.

Publications

Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy.

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