Cerebral amyloid angiopathy: Both viper and maggot in the brain

2005 ◽  
Vol 58 (3) ◽  
pp. 348-350 ◽  
Author(s):  
Roy O. Weller ◽  
James A. R. Nicoll
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Amyloid Angiopathy ◽  
Cerebral Amyloid ◽  
The Brain

scholarly journals Endothelial expression of human APP leads to cerebral amyloid angiopathy in mice

2020 ◽  
Author(s):  
Yuriko Tachida ◽  
Saori Miura ◽  
Rie Imamaki ◽  
Naomi Ogasawara ◽  
Hiroyuki Takuwa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Cerebral Amyloid Angiopathy ◽  
Amyloid Β ◽  
Blood Levels ◽  
Amyloid Angiopathy ◽  
Disease Mechanisms ◽  
Age Dependent ◽  
Cerebral Amyloid ◽  
The Brain

AbstractThe deposition of amyloid β (Aβ) in blood vessels of the brain, known as cerebral amyloid angiopathy (CAA), is observed in more than 90% of Alzheimer’s disease (AD) patients. The presence of such CAA pathology is not as evident, however, in most mouse models of AD, thereby making it difficult to examine the contribution of CAA to the pathogenesis of AD. Since blood levels of soluble amyloid precursor protein (sAPP) in rodents are less than 1% of those in humans, we hypothesized that endothelial APP expression would be markedly lower in rodents, thus providing a reason for the poorly expressed CAA pathology. Here we generated mice that specifically express human APP770 in endothelial cells. These mice exhibited an age-dependent robust deposition of Aβ in brain blood vessels but not in the parenchyma. Crossing these animals with APP knock-in mice led to an expanded CAA pathology as evidenced by increased amounts of amyloid accumulated in the cortical blood vessels. These results show that both neuronal and endothelial APP contribute cooperatively to vascular Aβ deposition, and suggest that this mouse model will be useful for studying disease mechanisms underlying CAA and for developing novel AD therapeutics.

083 Response to immunosuppressive therapy in cerebral amyloid angiopathy-related inflammation

2018 ◽  
Vol 89 (6) ◽  
pp. A33.3-A34
Author(s):  
Jasmin Tilling ◽  
Benjamin Trewin ◽  
Stanley Levy
Keyword(s):  
White Matter ◽  
Cognitive Decline ◽  
Cerebral Amyloid Angiopathy ◽  
White Matter Hyperintensities ◽  
Neurological Deficits ◽  
Amyloid Angiopathy ◽  
Dramatic Improvement ◽  
Age Related ◽  
Cerebral Amyloid ◽  
The Brain

IntroductionCerebral amyloid angiopathy (CAA) is a common age-related condition characterised by amyloid beta-peptide deposition affecting the medium sized cortical and leptomeningeal arteries, arterioles and capillaries. CAA-related Inflammation (CAA-I) is an increasingly recognised variant of CAA, which is thought to be due to perivascular auto-inflammation in response to amyloid deposition. We describe the clinical course of two cases of probable CAA-I.CasesA 71 year old man presented with new-onset seizures, headaches and subacute cognitive decline. MRI of the brain demonstrated confluent subcortical T2 white matter hyperintensities and cerebral oedema, with predominantly superimposed widespread cortico-subcortical micro-haemorrhages, in keeping with the diagnosis of CAA-I. A course of immunosuppresive therapy was commenced with five days of intravenous methylprednisolone, resulting in marked radiological and clinical improvement within two weeks.A 76 year old female presented with subacute cognitive dysfunction and apraxia, and transient left-sided weakness. MRI scan of the brain initially demonstrated a right temporo-occipital infarct, leading to primary treatment for stroke, but subsequently evolved to reveal diffuse multi-lobar T2 white matter hyperintensities with leptomeningeal involvement. A provisional diagnosis of CAA-I was made and following a poor clinical response to a trial of corticosteroid therapy, treatment with intravenous cyclophosphamide was commenced.ConclusionThese cases emphasise the importance of CAA-I as part of the differential diagnosis in patients presenting with symptoms of subacute cognitive decline, seizures, headaches and focal neurological deficits, given the potential for dramatic improvement with readily accessible immunosuppressive therapies.

99mTc-labeled benzothiazole and stilbene derivatives as imaging agents for Aβ plaques in cerebral amyloid angiopathy

MedChemComm ◽  
2014 ◽  
Vol 5 (2) ◽  
pp. 153-158 ◽  
Author(s):  
Jianhua Jia ◽  
Mengchao Cui ◽  
Jiapei Dai ◽  
Xuedan Wang ◽  
Yu-Shin Ding ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cerebral Amyloid Angiopathy ◽  
Spect Imaging ◽  
Imaging Agents ◽  
Amyloid Angiopathy ◽  
Stilbene Derivatives ◽  
Cerebral Amyloid ◽  
The Brain

99mTc-labeled probes in this study for the Aβ plaques in the blood vessels of the brain may be used as SPECT imaging agents for the diagnosis of CAA.

scholarly journals Mapping of Microvascular Architecture in the Brain of an Alzheimer’s Disease Mouse Model using MRI

2020 ◽  
Author(s):  
Suk-Ki Chang ◽  
JeongYeong Kim ◽  
DongKyu Lee ◽  
Chang Hyun Yoo ◽  
Seokha Jin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebral Amyloid Angiopathy ◽  
Brain Atlas ◽  
Amyloid Angiopathy ◽  
Relaxation Rates ◽  
Cerebral Microvasculature ◽  
Microvascular Architecture ◽  
Cerebral Amyloid ◽  
The Brain

Abstract Purpose Growing evidence suggests that alterations of the cerebral microvasculature play a critical role in the pathogenesis of Alzheimer’s disease (AD). The objective of this study was to characterize and evaluate the cerebral microvascular architecture in the AD transgenic (Tg) mice model compared with non-Tg mice using brain microvascular indices obtained by MRI.Methods Seven non-Tg mice and ten 5xFAD Tg mice were scanned using a 7-T animal MRI system to measure the transverse relaxation rates of R2 and R2* before and after injection of the monocrystalline iron oxide nanoparticle contrast agent. After calculation of the relaxation rate difference of ΔR2* and ΔR2, the microvascular indices of the vessel size index (VSI), mean vessel diameter (mVD), mean vessel density (Q), mean vessel-weighted image (MvWI), and blood volume fraction (BVf) were mapped. The voxel-based analyses and regions-of-interest (ROIs)-based analyses were performed to compare the indices between the non-Tg and Tg groups.Results The BVf, mVD, VSI, and MvWI were greater in the Tg group than in the non-Tg group based on voxel comparisons. Additionally, the ROIs-based analysis showed that ΔR2*, BVf, mVD, MvWI, and VSI were increased in the Tg group compared to the non-Tg group in several brain regions. Most ROIs defined by the mouse brain atlas were not significantly different between the two groups.Conclusion We found increased microvascular indices of VSI and mVD in the Tg mice, reflecting microvascular disruption in the brain, which may be related to damages of the neurovascular unit in AD caused by cerebral amyloid angiopathy.Clinical Relevance / Application: To date, few studies have investigated the microvascular injuries of the AD brain using MRI. We suggest that investigation of cerebral microvasculature using a high-field MRI in AD would be worthwhile to elucidate the pathophysiology of cerebral amyloid angiopathy in this disease. Indeed, microvascular MRI can be a promising imaging tool for investigating early diagnosis and monitoring treatment in AD.

scholarly journals Advances in our Understanding of the Pathophysiology, Detection and Management of Cerebral Amyloid Angiopathy

2012 ◽  
Vol 7 (2) ◽  
pp. 134 ◽  
Author(s):  
Octavio M Pontes-Neto ◽  
Eitan Auriel ◽  
Steven M Greenberg ◽  
◽  
◽  
...  
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Small Vessel Disease ◽  
Specific Treatment ◽  
Amyloid Β ◽  
Amyloid Angiopathy ◽  
Amyloid Β Peptide ◽  
Small Vessels ◽  
The Media ◽  
Cerebral Amyloid ◽  
The Brain

Cerebral amyloid angiopathy (CAA) is pathologically defined as the deposition of amyloid protein, most commonly the amyloid β peptide (Aβ), primarily within the media and adventitia of small and medium-sized arteries of the leptomeninges, cerebral and cerebellar cortex. This deposition likely reflects an imbalance between Aβ production and clearance within the brain and leads to weakening of the overall structure of brain small vessels, predisposing patients tolobar intracerebral haemorrhage (ICH), brain ischaemia and cognitive decline. CAA is associated with markers of small vessel disease, like lobar microbleeds and white matter hyperintensities on magnetic resonance imaging. Therefore, it can be now be diagnosed during life with reasonable accuracy by clinical and neuroimaging criteria. Despite the lack of a specific treatment for this condition, the detection of CAA may help in the management of patients, regarding the prevention of major haemorrhagic complications and genetic counselling. This review discusses recent advances in our understanding of the pathophysiology, detection and management of CAA.

Abstract 62: Increased Monocyte/Macrophage Pro-Inflammatory Cytokines and Chemokines in Mice With Cerebral Amyloid Angiopathy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Carson Finger ◽  
Juneyoung Lee ◽  
Diego Morales ◽  
Bharti Manwani
Keyword(s):  
Inflammatory Cytokines ◽  
Cerebral Amyloid Angiopathy ◽  
Neuronal Damage ◽  
Muscle Layer ◽  
Amyloid Angiopathy ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cerebral Amyloid ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Introduction: Cerebral amyloid angiopathy (CAA) is one of the common causes of intracerebral hemorrhage in the elderly. It is caused by the deposition of amyloid-beta1-40 (Aβ1-40) deposition within cerebral blood vessels, especially the smooth muscle layer, that can cause cerebral microbleeds (CMBs) and cognitive impairment. We hypothesize Aβ deposition causes an innate inflammatory response characterized by an increase and activation of microglia and macrophages. This inflammation might cause CMBs, neuronal damage and cognitive decline CAA. Methods: C57BL6 Tg-SwDI male and female mice (18 months) were used as a mouse model for CAA. Age-matched wild-type (WT) mice were used as controls. Brain samples from these mice were fractionated and 23-plex cytokine multiplex was performed on the brain lysates. Data was analyzed using two sample t-test or GraphPad PRISM. Results: Our data showed that CAA increased levels of pro-inflammatory cytokines in the brain, as compared with WT mice. Multiplex analysis showed that Tg-SwDI mice had significantly higher levels of cytokines; tumor necrosis factor-α (TNF-α; 54.38 vs. 17.03 pg/ml, p=0.00207), IL-12 (70.81 vs. 53.95 pg/ml, p= 0.014), macrophage inflammatory protein-1α (MIP-1α, 113.92 vs. 16.81 pg/ml, p=3.85E-10), MIP-1β (86.15 vs. 53.43 pg/ml, p= 3.51E-09) and monocyte chemoattractant protein-1 (MCP-1, 109.46 vs. 118.53 pg/ml, p= 0.00033). Conclusion: This study highlights a monocyte/macrophage driven pro-inflammatory milieu in CAA. Recent studies using in vivo two-photon imaging and histology have found recruitment of microglia and monocytes/macrophages around induced 100 μm sized hemorrhage. The increase in these microglia is only found in Alzheimer’s patients who also had CAA and was not seen in patients with no CAA, suggesting the role of microglia in causing vascular frailty in CAA. Our study suggests that pro-inflammatory cytokines like TNF-a, IL-12, MIP-1α, MIP-1β and MCP-1 can be therapeutic targets for CAA.

scholarly journals Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

2019 ◽  
Vol 116 (20) ◽  
pp. 10031-10038 ◽  
Author(s):  
Takayuki Inoue ◽  
Satoshi Saito ◽  
Masashi Tanaka ◽  
Hajime Yamakage ◽  
Toru Kusakabe ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Amyloid Angiopathy ◽  
Apoptotic Cell ◽  
Amyloid Β ◽  
Myeloid Cell ◽  
Low Permeability ◽  
Amyloid Angiopathy ◽  
Neuroprotective Effects ◽  
Cerebral Amyloid ◽  
The Brain

Cerebral amyloid angiopathy (CAA) results from amyloid-β deposition in the cerebrovasculature. It is frequently accompanied by Alzheimer’s disease and causes dementia. We recently demonstrated that in a mouse model of CAA, taxifolin improved cerebral blood flow, promoted amyloid-β removal from the brain, and prevented cognitive dysfunction when administered orally. Here we showed that taxifolin inhibited the intracerebral production of amyloid-β through suppressing the ApoE–ERK1/2–amyloid-β precursor protein axis, despite the low permeability of the blood–brain barrier to taxifolin. Higher expression levels of triggering receptor expressed on myeloid cell 2 (TREM2) were associated with the exacerbation of inflammation in the brain. Taxifolin suppressed inflammation, alleviating the accumulation of TREM2-expressing cells in the brain. It also mitigated glutamate levels and oxidative tissue damage and reduced brain levels of active caspases, indicative of apoptotic cell death. Thus, the oral administration of taxifolin had intracerebral pleiotropic neuroprotective effects on CAA through suppressing amyloid-β production and beneficially modulating proinflammatory microglial phenotypes.

scholarly journals A case of mr imaging detection of hemorrhages in cerebral amyloid angiopathy

Pulse ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 53-55
Author(s):  
FA Ruby ◽  
S Ahsan ◽  
MJ Chandy ◽  
J Alam
Keyword(s):  
Cerebral Amyloid Angiopathy ◽  
Recurrent Stroke ◽  
Cerebral Hemispheres ◽  
Amyloid Angiopathy ◽  
Mild Renal Impairment ◽  
Imaging Detection ◽  
Cerebral Amyloid ◽  
The Brain ◽  
P 53

A 70-year-old diabetic and hypertensive male patient with mild renal impairment presented with recurrent stroke. CT scan of brain demonstrated acute hemorrhagic / nonhemorrhagic infarcts in the brain. Gradient sequences in the follow-up MRI showed extensive blooming in the cortex of both cerebral hemispheres. There were multiple foci of blooming in basal ganglia and cerebellar hemispheres. Hemosiderin staining was present in posterior fossa. MR findings were consistent with extensive primary cerebral amyloid angiopathy (CAA).Pulse Vol.7 January-December 2014 p.53-55

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