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Cerebral amyloid angiopathy

Susanne J van Veluw, Hugo J Kuijf, Andreas Charidimou, Anand Viswanathan, Geert Jan Biessels, Annemieke J M Rozemuller, Matthew P Frosch, Steven M Greenberg
Microhemorrhages are strongly associated with advanced cerebral amyloid angiopathy (CAA). Although it has been frequently proposed that the deposition of Aβ in the walls of cortical vessels directly causes microhemorrhages, this has not been studied in great detail, mainly because the ruptured vessels are often missed on routine histopathologic examination. Here, we examined histopathological data from studies targeting microhemorrhages with high-resolution ex vivo 7 T MRI in nine cases with moderate-to-severe CAA, and assessed the presence of Aβ in the walls of involved vessels...
October 22, 2016: Acta Neuropathologica
Przemyslaw Jurczak, Patrick Groves, Aneta Szymanska, Sylwia Rodziewicz-Motowidlo
Human cystatin C (hCC) is a small protein belonging to the cystatin family of papain-like cysteine proteinase inhibitors. We review the recent literature concerning structural aspects of hCC related to disease. We focus on the mechanisms of hCC dimerization, oligomerization and amyloid formation. Amyloid formation is associated with a number of neurodegenerative diseases that affect the independence and quality of life of aging populations. hCC is one of the second wave proteins that have been found to undergo amyloidosis associated with disease...
October 19, 2016: FEBS Letters
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Elisanne Alm Biemans, Lieke Jäkel, Robert Mw de Waal, H Bea Kuiperij, Marcel M Verbeek
Alzheimer's disease and cerebral amyloid angiopathy are characterized by accumulation of amyloid-β (Aβ) at the cerebrovasculature due to decreased clearance at the blood-brain barrier (BBB). However, the exact mechanism of Aβ clearance across this barrier has not been fully elucidated. The hCMEC/D3 cell line has been characterized as a valid model for the BBB. In this study we evaluated the use of this model to study Aβ clearance across the BBB, with an emphasis on brain-to-blood directional permeability...
October 11, 2016: Journal of Neuroscience Research
Alex E Roher, Chera L Maarouf, Tyler A Kokjohn, Christine Belden, Geidy Serrano, Marwan S Sabbagh, Thomas G Beach
INTRODUCTION: Based on the amyloid cascade hypothesis of Alzheimer's disease (AD) pathogenesis, a series of clinical trials involving immunotherapies have been undertaken including infusion with the IgG1 monoclonal anti-Aβ antibody solanezumab directed against the middle of the soluble Aβ peptide. In this report, we give an account of the clinical history, psychometric testing, gross and microscopic neuropathology as well as immunochemical quantitation of soluble and insoluble Aβ peptides and other proteins of interest related to AD pathophysiology in a patient treated with solanezumab...
2016: American Journal of Neurodegenerative Disease
T A Polyakova, A V Arablinsky, O S Levin
The role of the cerebral microbleeds (CMB) as a potential predictor of hemorrhagic complications of thrombolytic therapy is discussed. CMB are small perivascular hemosiderin deposits in the brain detected by magnetic resonance imaging in gradient echo T2* or SWI sequences. They are associated (along with leukoaraiosis or lacunes) with cerebral microangiopathies. Most often CMB are associated with hypertensive arteriopathy (the main cause of CMB localization) or cerebral amyloid angiopathy (the main cause of cerebral CMB)...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
R J Kryscio, E L Abner, P T Nelson, D Bennett, J Schneider, L Yu, L S Hemmy, K O Lim, K Masaki, N Cairns, C Xiong, R Woltjer, H H Dodge, S Tyas, D W Fardo, W Lou, L Wan, F A Schmitt
BACKGROUND: Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. OBJECTIVE: To correlate measures of cerebral vascular pathology with cognitive trajectories. SETTING: Observational study. PARTICIPANTS: A cohort of 2,274 individuals who came to autopsy at a mean age of 89...
June 2016: Journal of Prevention of Alzheimer's Disease
Duangnapa Roongpiboonsopit, Andreas Charidimou, Christopher M William, Arne Lauer, Guido J Falcone, Sergi Martinez-Ramirez, Alessandro Biffi, Alison Ayres, Anastasia Vashkevich, Oluwole O Awosika, Jonathan Rosand, M Edip Gurol, Scott B Silverman, Steven M Greenberg, Anand Viswanathan
OBJECTIVE: To identify predictors of early lobar intracerebral hemorrhage (ICH) recurrence, defined as a new ICH within 6 months of the index event, in patients with cerebral amyloid angiopathy (CAA). METHODS: Participants were consecutive survivors (age ≥55 years) of spontaneous symptomatic probable or possible CAA-related lobar ICH according to the Boston criteria, drawn from an ongoing single-center cohort study. Neuroimaging markers ascertained in CT or MRI included focal (≤3 sulci) or disseminated (>3 sulci) cortical superficial siderosis (cSS), acute convexity subarachnoid hemorrhage (cSAH), cerebral microbleeds, white matter hyperintensities burden and location, and baseline ICH volume...
September 30, 2016: Neurology
Franz Fazekas, Marieke J H Wermer
No abstract text is available yet for this article.
September 30, 2016: Neurology
Shimpei Iikuni, Masahiro Ono, Hiroyuki Watanabe, Masashi Yoshimura, Hatsue Ishibashi-Ueda, Masafumi Ihara, Hideo Saji
Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid aggregates in the walls of the cerebral vasculature. Recently, the development of molecular imaging probes targeting CAA has been attracting much attention. We previously reported the 99mTc-hydroxamamide (99mTc-Ham) complex with a bivalent benzothiazole scaffold as a binding moiety for amyloid aggregates ([99mTc]BT2) and its utility for CAA-specific imaging. However, the simultaneous generation of two radiolabeled complexes derived from the geometric isomers was observed in the 99mTc-labeling reaction...
2016: PloS One
Slađan Nešić, Vladimir Kukolj, Darko Marinković, Ivana Vučićević, Milijan Jovanović
BACKGROUND: Cerebral amyloid angiopathy (CAA) is a disorder characterized by amyloid deposition in the wall of cerebral blood vessels. The deposits of amyloid occur frequently in the blood vessels of the frontal, parietal and occipital cortex. OBJECTIVE: To examine the characteristics of CAA classified according to the Vonsattel scale in elderly dogs histologically and immunohistochemically as well as the semi-quantitative evaluation of the amyloid deposits in the different segments of the brain...
September 26, 2016: Veterinary Quarterly
Nienke M de Wit, Hripsime Snkhchyan, Sandra den Hoedt, Darcos Wattimena, Rob de Vos, Monique T Mulder, Jochen Walter, Pilar Martinez-Martinez, Jeroen J Hoozemans, Annemieke J Rozemuller, Helga E de Vries
BACKGROUND: The majority of patients with Alzheimer's disease (AD) exhibit amyloid-β (Aβ) deposits at the brain vasculature, a process referred to as cerebral amyloid angiopathy (CAA). In over 51% of AD cases, Aβ also accumulates in cortical capillaries, which is termed capillary CAA (capCAA). It has been postulated that the presence of capCAA in AD is a specific subtype of AD, although underlying mechanisms are not yet fully understood. Sphingolipids (SLs) are implicated in neurodegenerative disorders, including AD...
September 21, 2016: Journal of Alzheimer's Disease: JAD
Susanne J van Veluw, Andreas Charidimou, Andre J van der Kouwe, Arne Lauer, Yael D Reijmer, Isabel Costantino, M Edip Gurol, Geert Jan Biessels, Matthew P Frosch, Anand Viswanathan, Steven M Greenberg
Cerebral amyloid angiopathy is a common neuropathological finding in the ageing human brain, associated with cognitive impairment. Neuroimaging markers of severe cerebral amyloid angiopathy are cortical microbleeds and microinfarcts. These parenchymal brain lesions are considered key contributors to cognitive impairment. Therefore, they are important targets for therapeutic strategies and may serve as surrogate neuroimaging markers in clinical trials. We aimed to gain more insight into the pathological basis of magnetic resonance imaging-defined microbleeds and microinfarcts in cerebral amyloid angiopathy, and to explore the pathological burden that remains undetected, by using high and ultra-high resolution ex vivo magnetic resonance imaging, as well as detailed histological sampling...
September 19, 2016: Brain: a Journal of Neurology
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Airton Leonardo de Oliveira Manoel, Alberto Goffi, Fernando Godinho Zampieri, David Turkel-Parrella, Abhijit Duggal, Thomas R Marotta, R Loch Macdonald, Simon Abrahamson
Spontaneous intracerebral hemorrhage (ICH), defined as nontraumatic bleeding into the brain parenchyma, is the second most common subtype of stroke, with 5.3 million cases and over 3 million deaths reported worldwide in 2010. Case fatality is extremely high (reaching approximately 60 % at 1 year post event). Only 20 % of patients who survive are independent within 6 months. Factors such as chronic hypertension, cerebral amyloid angiopathy, and anticoagulation are commonly associated with ICH. Chronic arterial hypertension represents the major risk factor for bleeding...
September 18, 2016: Critical Care: the Official Journal of the Critical Care Forum
Michelle R Caunca, Victor Del Brutto, Hannah Gardener, Nirav Shah, Nelly Dequatre-Ponchelle, Ying Kuen Cheung, Mitchell S V Elkind, Truman R Brown, Charlotte Cordonnier, Ralph L Sacco, Clinton B Wright
BACKGROUND: Cerebral microbleeds (CMBs) represent intracerebral hemorrhages due to amyloid angiopathy or exposure to modifiable risk factors. Few community-based stroke-free studies including blacks and Hispanics have been done. METHODS AND RESULTS: The Northern Manhattan Study (NOMAS) is a stroke-free, racially and ethnically diverse cohort study. Brain MRI was performed in 1290 participants, 925 of whom had available T2* gradient-recall echo data. We used multivariable logistic regression to examine the association of sociodemographics, vascular risk factors, apolipoprotein E (APOE) genotype, and brain MRI markers with CMB presence and location...
September 2016: Journal of the American Heart Association
Chih-Ping Chung, Kun-Hsien Chou, Wei-Ta Chen, Li-Kuo Liu, Wei-Ju Lee, Liang-Kung Chen, Ching-Po Lin, Pei-Ning Wang
BACKGROUND AND PURPOSE: Different distributions of cerebral microbleeds (CMBs) are associated with distinct pathological mechanisms. Lobar CMBs are thought to be related to cerebral amyloid angiopathy, whereas deep or infratentorial CMBs are related to hypertensive vasculopathy. The present study aimed to evaluate the effects of CMBs and their locations on a variety of cognitive domains. METHODS: Study subjects were selected from the community-based I-Lan Longitudinal Aging Study...
October 2016: Stroke; a Journal of Cerebral Circulation
Nicolae Sarbu, Robert Y Shih, Robert V Jones, Iren Horkayne-Szakaly, Laura Oleaga, James G Smirniotopoulos
White matter diseases include a wide spectrum of disorders that have in common impairment of normal myelination, either by secondary destruction of previously myelinated structures (demyelinating processes) or by primary abnormalities of myelin formation (dysmyelinating processes). The pathogenesis of many white matter diseases remains poorly understood. Demyelinating disorders are the object of this review and will be further divided into autoimmune, infectious, vascular, and toxic-metabolic processes. Autoimmune processes include multiple sclerosis and related diseases: tumefactive demyelinating lesions, Balo concentric sclerosis, Marburg and Schilder variants, neuromyelitis optica (Devic disease), acute disseminated encephalomyelitis, and acute hemorrhagic leukoencephalopathy (Hurst disease)...
September 2016: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Arne Lauer, Susanne J van Veluw, Christopher M William, Andreas Charidimou, Duangnapa Roongpiboonsopit, Anastasia Vashkevich, Alison Ayres, Sergi Martinez-Ramirez, Edip M Gurol, Geert Jan Biessels, Matthew Frosch, Steven M Greenberg, Anand Viswanathan
OBJECTIVES: To identify in vivo MRI markers that might correlate with cerebral microinfarcts (CMIs) on autopsy in patients with cerebral amyloid angiopathy (CAA). METHODS: We included patients with neuropathologic evidence of CAA on autopsy and available antemortem brain MRI. Clinical characteristics and in vivo MRI markers of CAA-related small vessel disease were recorded, including white matter hyperintensities, cerebral microbleeds, cortical superficial siderosis, and centrum semiovale perivascular spaces...
October 4, 2016: Neurology
F Schöberl, O E Eren, F A Wollenweber, T Kraus, L Kellert
Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease in the elderly. Neuropathologically, it is characterized by deposition of amyloid-ß (Aß) in the wall of small to medium-sized arteries, capillaries and venules of the cerebral cortex and leptomeninges. Over the last years it was recognized as an important cause of spontaneous intracerebral hemorrhage and cognitive deficits in the elderly. The clinical and radiological manifestations are diverse ranging from acute onset focal neurological deficits due to intracerebral lobar hemorrhage to subacute progressive cognitive impairment due to Aß-mediated inflammation confluent subcortical edema...
September 2016: Fortschritte der Neurologie-Psychiatrie
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