scholarly journals Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques

Metallomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 539-546 ◽  
Author(s):  
Xiayoue Zhu ◽  
Tiffany W. Victor ◽  
Ashwin Ambi ◽  
Joseph K. Sullivan ◽  
Joshua Hatfield ◽  
...  
Keyword(s):  
Multimodal Imaging ◽  
Amyloid Plaques ◽  
Copper Accumulation ◽  
Amyloid Angiopathy ◽  
Imaging Studies ◽  
Brain Vessels ◽  
Aβ Amyloid ◽  
Cerebral Amyloid ◽  
Copper Chelators ◽  
Tg2576 Mice

Multimodal imaging studies show that Aβ amyloid in brain vessels of Tg2576 mice (green) preferentially binds copper (red) – a pathology that can be reduced with copper chelators.

scholarly journals Hereditary cerebral amyloid angiopathy, Piedmont-type mutation

2020 ◽  
Vol 6 (2) ◽  
pp. e411 ◽  
Author(s):  
Mariel G. Kozberg ◽  
Susanne J. van Veluw ◽  
Matthew P. Frosch ◽  
Steven M. Greenberg
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Amyloid Angiopathy ◽  
Pathologic Examination ◽  
Potential Association ◽  
History Of ◽  
Intracerebral Hemorrhages ◽  
Β Amyloid ◽  
Cerebral Amyloid

ObjectiveWe present here a case report of a patient with a family history of intracerebral hemorrhages (ICHs) who presented with multiple large lobar hemorrhages in rapid succession, with cognitive sparing, who was found to have a mutation in the β-amyloid coding sequence of amyloid precursor protein (Leu705Val), termed the Piedmont-type mutation, the second ever reported case of this form of hereditary cerebral amyloid angiopathy (CAA).MethodsTargeted pathologic examination was performed aided by the use of ex vivo MRI.ResultsSevere CAA was observed mainly involving the leptomeningeal vessels and, to a far lesser extent, cortical vessels, with no amyloid plaques or neurofibrillary tangles.ConclusionsThis leptomeningeal pattern of β-amyloid deposition coupled with multiple large hemorrhages demonstrates unique pathophysiologic characteristics of CAA associated with the Piedmont-type mutation, suggesting a potential association between leptomeningeal CAA and larger ICHs.

scholarly journals Advances in cerebral amyloid angiopathy imaging

2019 ◽  
Vol 12 ◽  
pp. 175628641984411 ◽  
Author(s):  
Szu-Ju Chen ◽  
Hsin-Hsi Tsai ◽  
Li-Kai Tsai ◽  
Sung-Chun Tang ◽  
Bo-Chin Lee ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Imaging Techniques ◽  
White Matter Hyperintensity ◽  
Superficial Siderosis ◽  
Clinical Aspects ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Imaging Studies ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease caused by β -amyloid (Aβ) deposition at the leptomeningeal vessel walls. It is a common cause of spontaneous intracerebral hemorrhage and a frequent comorbidity in Alzheimer’s disease. The high recurrent hemorrhage rate in CAA makes it very important to recognize this disease to avoid potential harmful medication. Imaging studies play an important role in diagnosis and research of CAA. Conventional computed tomography and magnetic resonance imaging (MRI) methods reveal anatomical alterations, and remains as the most reliable tool in identifying CAA according to modified Boston criteria. The vascular injuries of CAA result in both hemorrhagic and ischemic manifestations and related structural changes on MRI, including cerebral microbleeds, cortical superficial siderosis, white matter hyperintensity, MRI-visible perivascular spaces, and cortical microinfarcts. As imaging techniques advance, not only does the resolution of conventional imaging improve, but novel skills in functional and molecular imaging studies also enable in vivo analysis of vessel physiological changes and underlying pathology. These modern tools help in early detection of CAA and may potentially serve as sensitive outcome markers in future clinical trials. In this article, we reviewed past studies of CAA focusing on utilization of various conventional and novel imaging techniques in both research and clinical aspects.

scholarly journals Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer’s brain tissue

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Marius Kollmer ◽  
William Close ◽  
Leonie Funk ◽  
Jay Rasmussen ◽  
Aref Bsoul ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Brain Tissue ◽  
Amyloid Fibrils ◽  
Structural Basis ◽  
Amyloid Angiopathy ◽  
Cryo Electron Microscopy ◽  
Aβ Amyloid ◽  
Cerebral Amyloid ◽  
Aβ Fibrils

Abstract The formation of Aβ amyloid fibrils is a neuropathological hallmark of Alzheimer’s disease and cerebral amyloid angiopathy. However, the structure of Aβ amyloid fibrils from brain tissue is poorly understood. Here we report the purification of Aβ amyloid fibrils from meningeal Alzheimer’s brain tissue and their structural analysis with cryo-electron microscopy. We show that these fibrils are polymorphic but consist of similarly structured protofilaments. Brain derived Aβ amyloid fibrils are right-hand twisted and their peptide fold differs sharply from previously analyzed Aβ fibrils that were formed in vitro. These data underscore the importance to use patient-derived amyloid fibrils when investigating the structural basis of the disease.

scholarly journals Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments

Stroke ◽  
2020 ◽  
Vol 51 (12) ◽  
pp. 3600-3607 ◽  
Author(s):  
Young Hee Jung ◽  
Hyemin Jang ◽  
Seong Beom Park ◽  
Yeong Sim Choe ◽  
Yuhyun Park ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Disease Burden ◽  
Dentate Nucleus ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Amyloid Angiopathy ◽  
Positron Emission ◽  
Aβ Amyloid ◽  
Cerebral Amyloid

Background and Purpose: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. Methods: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. Results: The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P <0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P =0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P =0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P =0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P =0.041) than the dentate group. Conclusions: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

scholarly journals P1-061: Cerebral encephalopathy with cerebral amyloid angiopathy and numerous amyloid plaques presenting aberrant low levels of CSF Aβ 40/1-42

2012 ◽  
Vol 8 (4S_Part_4) ◽  
pp. P127-P128
Author(s):  
Kimitoshi Hirayanagi ◽  
Masaki Ikeda ◽  
Motonobu Arai ◽  
Satoko Kakuda ◽  
Kouki Makioka ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Plaques ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Low Levels

scholarly journals Metal complexes for multimodal imaging of misfolded protein-related diseases

2017 ◽  
Vol 46 (42) ◽  
pp. 14461-14474 ◽  
Author(s):  
S. Lacerda ◽  
J.-F. Morfin ◽  
C. F. G. C. Geraldes ◽  
É. Tóth
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Metal Complexes ◽  
Cerebral Amyloid Angiopathy ◽  
Type Ii Diabetes ◽  
Multimodal Imaging ◽  
Amyloid Angiopathy ◽  
Misfolded Protein ◽  
Type Ii ◽  
Cerebral Amyloid ◽  
Lateral Sclerosis

Aggregation of misfolded proteins and progressive polymerization of otherwise soluble proteins is a common hallmark of several highly debilitating and increasingly prevalent diseases, including amyotrophic lateral sclerosis, cerebral amyloid angiopathy, type II diabetes and Parkinson's, Huntington's and Alzheimer's diseases.

scholarly journals Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 72
Author(s):  
Anna Bonaterra-Pastra ◽  
Sofia Fernández-de-Retana ◽  
Andrea Rivas-Urbina ◽  
Núria Puig ◽  
Sònia Benítez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Profile ◽  
Cerebral Amyloid Angiopathy ◽  
Chronic Phase ◽  
Amyloid Angiopathy ◽  
Brain Vessels ◽  
Control Subjects ◽  
Cerebral Amyloid ◽  
Lipoprotein Composition

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer’s disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation.

scholarly journals Cerebral Amyloid Angiopathy Increases Susceptibility to Infarction After Focal Cerebral Ischemia in Tg2576 Mice

Stroke ◽  
2014 ◽  
Vol 45 (10) ◽  
pp. 3064-3069 ◽  
Author(s):  
Eric Milner ◽  
Meng-Liang Zhou ◽  
Andrew W. Johnson ◽  
Ananth K. Vellimana ◽  
Jacob K. Greenberg ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Amyloid Angiopathy ◽  
Focal Cerebral Ischemia ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Tg2576 Mice

scholarly journals Experimental hypertension increases spontaneous intracerebral hemorrhages in a mouse model of cerebral amyloidosis

2015 ◽  
Vol 36 (2) ◽  
pp. 399-404 ◽  
Author(s):  
Giselle F Passos ◽  
Kelley Kilday ◽  
Daniel L Gillen ◽  
David H Cribbs ◽  
Vitaly Vasilevko
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse Model ◽  
Experimental Hypertension ◽  
Amyloid Angiopathy ◽  
Similar Increase ◽  
Cerebral Amyloidosis ◽  
Intracerebral Hemorrhages ◽  
Cerebral Amyloid ◽  
And Control ◽  
Tg2576 Mice

Hypertension and cerebral amyloid angiopathy (CAA) are major risk factors for intracerebral hemorrhage (ICH); however the mechanisms of interplay between the two are not fully understood. We investigated the effect of hypertension in a transgenic mouse model with Alzheimer’s-like pathology (Tg2576) treating them with angiontensin II and L-NG-nitroarginine methyl ester. A similar increase in systolic blood pressure was observed in both Tg2576 and control mice; however Tg2576 mice developed signs of stroke with a markedly shorter latency. Cerebral deposition of amyloid beta promotes the hypertension-induced ICH, thus supporting the notion that hypertension is a risk factor for ICH among patients with CAA.

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