scholarly journals Animal models of cerebral amyloid angiopathy

2017 ◽  
Vol 131 (19) ◽  
pp. 2469-2488 ◽  
Author(s):  
Lieke Jäkel ◽  
William E. Van Nostrand ◽  
James A.R. Nicoll ◽  
David J. Werring ◽  
Marcel M. Verbeek
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Cerebral Amyloid Angiopathy ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Transgenic Mouse Models ◽  
Ethical Considerations ◽  
Naturally Occurring ◽  
Cerebral Amyloid

Cerebral amyloid angiopathy (CAA), due to vascular amyloid β (Aβ) deposition, is a risk factor for intracerebral haemorrhage and dementia. CAA can occur in sporadic or rare hereditary forms, and is almost invariably associated with Alzheimer’s disease (AD). Experimental (animal) models are of great interest in studying mechanisms and potential treatments for CAA. Naturally occurring animal models of CAA exist, including cats, dogs and non-human primates, which can be used for longitudinal studies. However, due to ethical considerations and low throughput of these models, other animal models are more favourable for research. In the past two decades, a variety of transgenic mouse models expressing the human Aβ precursor protein (APP) has been developed. Many of these mouse models develop CAA in addition to senile plaques, whereas some of these models were generated specifically to study CAA. In addition, other animal models make use of a second stimulus, such as hypoperfusion or hyperhomocysteinemia (HHcy), to accelerate CAA. In this manuscript, we provide a comprehensive review of existing animal models for CAA, which can aid in understanding the pathophysiology of CAA and explore the response to potential therapies.

MEMANTINE ATTENUATES VASCULAR AMYLOID β DEPOSITS AND SPONTANEOUS HEMORRHAGES IN MOUSE MODELS OF CEREBRAL AMYLOID ANGIOPATHY

2017 ◽  
Vol 13 (7) ◽  
pp. P917-P918 ◽  
Author(s):  
Yasuteru Inoue ◽  
Mitsuharu Ueda ◽  
Teruaki Masuda ◽  
Yohei Misumi ◽  
Taro Yamashita ◽  
...  
Keyword(s):  
Mouse Models ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid

scholarly journals Progression of Cerebral Amyloid Angiopathy in Transgenic Mouse Models of Alzheimer Disease

2005 ◽  
Vol 64 (7) ◽  
pp. 588-594 ◽  
Author(s):  
Sarah B Domnitz ◽  
Elissa M Robbins ◽  
Alex W Hoang ◽  
Monica Garcia-Alloza ◽  
Bradley T Hyman ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Transgenic Mouse Models ◽  
Cerebral Amyloid

scholarly journals Cerebrospinal fluid levels of the neurotrophic factor neuroleukin are increased in early Alzheimer’s disease, but not in cerebral amyloid angiopathy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna M. De Kort ◽  
H. Bea Kuiperij ◽  
Daniel Alcolea ◽  
Iris Kersten ◽  
Alexandra A. M. Versleijen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cerebral Amyloid Angiopathy ◽  
Medical Center ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
Neuro Inflammation

Abstract Background Neuroleukin (NLK) is a protein with neurotrophic properties and is present in a proportion of senile plaques and amyloid laden vessels. It has been suggested that NLK is part of a neuroprotective response to amyloid β-induced cell death. The aim of our study was to investigate the value of cerebrospinal fluid (CSF) NLK levels as a biomarker of vascular amyloid deposition in patients with cerebral amyloid angiopathy (CAA) and in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Methods CSF NLK levels were quantified by ELISA in CAA patients (n = 25) and controls (n = 27) and in two independent samples of aMCI patients, AD patients, and controls: (1) From the Radboud University Medical Center (Nijmegen), we included n = 19 aMCI patients, n = 40 AD patients, and n = 32 controls. (2) From the Hospital of Sant Pau (Barcelona), we included n = 33 aMCI patients, n = 17 AD patients, and n = 50 controls. Results CSF NLK levels were similar in CAA patients and controls (p = 0.95). However, we found an elevated CSF concentration of NLK in aMCI (p < 0.0001) and AD patients (p < 0.0001) compared to controls in both samples sets. In addition, we found a correlation of CSF NLK with CSF YKL-40 (age-adjusted-spearman-rank-coefficient = 0.82, p < 0.0001) in aMCI/AD patients, a well-known glial marker of neuro-inflammation. Conclusions We found that CSF NLK levels are elevated in aMCI and AD patients compared to controls, but are not increased in CAA patients. CSF NLK levels may be related to an increased neuroinflammatory state in early stages of AD, given its association with YKL-40.

scholarly journals Cerebral amyloid angiopathy and comparative analysis of amyloid-β protein in birds

2018 ◽  
Author(s):  
Yumi Une ◽  
Mutsumi Yamazaki ◽  
Maho Morimoto ◽  
Fuyuki Kametani ◽  
Dennilyn Parker ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Cerebral Amyloid Angiopathy ◽  
Senile Plaques ◽  
Neurofibrillary Tangle ◽  
Bird Species ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Amyloid Β Protein ◽  
Cerebral Amyloid

Senile plaques and cerebral amyloid angiopathy (CAA)?are well-documented in various mammals, and several species even exhibit neurofibrillary tangle (NFT). However, we know far less about whether such symptoms are present in birds. Therefore, here we clarified the occurrence and pathogenesis of avian aβ-related lesions, analyzing the aβ amino-acid sequence across 28 birds at multiple life stages, representing 15 species, 14 genera, and 9 nine families.?We also determined the expected aβ amino-acid sequence after comparing data from the brains of nine birds (seven species) with publicly available NCBI data. We observed CAA and senile plaque-like deposition only in a female Amazon parrot, estimated to be around 30–40 years old. We identified two Aβ depositions (40 and 42) in the same location that correspond to Aβ 6-42. Additionally, we observed severe Aβ deposition, accompanied by severe hemorrhaging, in blood vessels of the superficial and deep portions of the brain. These lesions were directly related to the cause of death. Of 40 bird species, 36 exhibited type 1 Aβ amino-acid sequences, similar to humans. Given that all of these birds were old, our results suggest that Aβ is deposited primarily as CAA as the animals age. This report is the first clinically based description of CAA in birds. Interspecific variation likely exists because we identified species that did not exhibit Aβ deposition even when the birds are old enough. However, even birds of the same taxonomic status differed in whether they possessed or lacked Aβ deposition. Thus, other factors besides Aβ amino-acid sequence could influence this symptom.

scholarly journals Cerebral amyloid angiopathy severity is linked to dilation of juxtacortical perivascular spaces

2015 ◽  
Vol 36 (3) ◽  
pp. 576-580 ◽  
Author(s):  
Susanne J van Veluw ◽  
Geert Jan Biessels ◽  
Willem H Bouvy ◽  
Wim GM Spliet ◽  
Jaco JM Zwanenburg ◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Perivascular Spaces ◽  
Resonance Imaging ◽  
Centrum Semiovale ◽  
Tissue Sections ◽  
Cortical Areas ◽  
Cerebral Amyloid

Perivascular spaces are an emerging marker of small vessel disease. Perivascular spaces in the centrum semiovale have been associated with cerebral amyloid angiopathy. However, a direct topographical relationship between dilated perivascular spaces and cerebral amyloid angiopathy severity has not been established. We examined this association using post-mortem magnetic resonance imaging in five cases with evidence of cerebral amyloid angiopathy pathology. Juxtacortical perivascular spaces dilation was evaluated on T2 images and related to cerebral amyloid angiopathy severity in overlying cortical areas on 34 tissue sections stained for Amyloid β. Degree of perivascular spaces dilation was significantly associated with cerebral amyloid angiopathy severity (odds ratio = 3.3, 95% confidence interval 1.3–7.9, p = 0.011). Thus, dilated juxtacortical perivascular spaces are a promising neuroimaging marker of cerebral amyloid angiopathy severity.

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