cerebral amyloid angiopathy inflammation

Since 1906, when Dr. Alois Alzheimer first described in a patient "a peculiar severe disease process of the cerebral cortex", people suffering from this pathology have been waiting for a breakthrough therapy. Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative brain disorder and the most common form of dementia in the elderly with a long presymptomatic phase. Worldwide, approximately 50 million people are living with dementia, with AD comprising 60-70% of cases. Pathologically, AD is characterized by the deposition of amyloid β-peptide (Aβ) in the neuropil (neuritic plaques) and blood vessels (amyloid angiopathy), and by the accumulation of hyperphosphorylated tau in neurons (neurofibrillary tangles) in the brain, with associated loss of synapses and neurons, together with glial activation, and neuroinflammation, resulting in cognitive deficits and eventually dementia...

Although preclinical research and observer studies on patients with atrial fibrillation concluded that direct oral anticoagulants (DOACs) can protect against dementia like Alzheimer's disease (AD), clinical investigation towards therapeutical approval is still pending. DOACs target pathological thrombin, which is, like toxic tau and amyloid-ß proteins (Aß), an early hallmark of AD. Especially in hippocampal and neocortical areas, the release of parenchymal Aß into the blood induces thrombin and proinflammatory bradykinin synthesis by activating factor XII of the contact system...

BACKGROUND AND OBJECTIVES: Amyloid-related imaging abnormalities suggestive of vasogenic edema or sulcal effusion (ARIA-E) are the most common adverse events complicating Alzheimer's disease (AD) immunotherapy with anti-amyloid-beta (Aβ) monoclonal antibodies (mAbs). ARIA-E can also occur spontaneously in cerebral amyloid angiopathy-related inflammation (CAA-ri), a rare autoimmune encephalopathy associated with increased cerebrospinal fluid (CSF) levels of anti-Aβ autoantibodies. Although the pathophysiological mechanisms of ARIA-E remain to be fully elucidated, experimental evidence from ex-vivo studies suggest that gantenerumab and aducanumab enable microglial activation...

PURPOSE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare potentially reversible encephalopathy associated with an autoimmune process against proteins deposited in the walls of cortical and leptomeningeal brain vessels. Definite diagnosis requires histopathological features of vascular inflammation and amyloid deposition from brain biopsy. Clinical-neuroradiological criteria have been recently introduced and validated to reduce the need for biopsy. The purpose of this paper is to report a historical retrospective review of clinical-neuroradiological follow-up of two patients with probable CAA-ri and five patients with a reasonably probable suspect of CAA-ri (4 females, 3 males, patient's age at admission: 66-79 years) seen at our institution between 2007 and 2021, focusing on clinical and neuroradiological awareness to this entity and variable response to immunotherapy...

BACKGROUND: Cerebral amyloid angiopathy is a cerebrovascular disease directly implicated in Alzheimer's disease pathogenesis through amyloid-β deposition. Growing evidence has shown a pivotal role of chronic neuroinflammation both in cerebral amyloid angiopathy and Alzheimer's disease. OBJECTIVE: The aim of this study was to investigate whether circulating levels of the complement 3, a crucial component of the innate immune system, are increased in patients with cerebral amyloid angiopathy...

Intracerebral hemorrhage (ICH) is a severe stroke with a high death rate (40% mortality). The prevalence of hemorrhagic stroke has increased globally, with changes in the underlying cause over time as anticoagulant use and hypertension treatment have improved. The fundamental etiology of ICH and the mechanisms of harm from ICH, particularly the complex interaction between edema, inflammation, and blood product toxicity, have been thoroughly revised by the American Heart Association (AHA) in 2022. Although numerous trials have investigated the best medicinal and surgical management of ICH, there is still no discernible improvement in survival and functional tests...

Cerebral small vessel diseases (CSVDs) are prominent contributors to vascular cognitive impairment and dementia and can arise from a range of etiologies. Cerebral amyloid angiopathy (CAA) and hypertension (HTN), both prevalent in the elderly population, lead to cerebral microhemorrhages, macrohemorrhages, and white matter damage. However, their respective underlying mechanisms and molecular events are poorly understood. Here, we show that the transgenic rat model of CAA type 1 (rTg-DI) exhibits perivascular inflammation that is lacking in the spontaneously hypertensive stroke-prone (SHR-SP) rat model of HTN...

Background: Cerebral amyloid angiopathy-related inflammation (CAA-I) presents with slowly progressive nonspecific neurological symptoms, such as headache, cognitive function disorder, and seizures. Pathologically, the deposition of amyloid-β proteins at the cortical vascular wall is a characteristic and definitive finding. Differential diagnoses include infectious encephalitis, neurosarcoidosis, primary central nervous system lymphoma, and glioma. Here, we report a case of CAA-I showing acute progression, suggesting a glioma without enhancement, in which a radiological diagnosis was difficult using standard magnetic resonance imaging...

β-amyloid (Aβ) deposits in brain blood vessel walls underlie the vascular pathology of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). Growing evidence has suggested the involvement of cerebrovascular dysfunction in the initiation and progression of cognitive impairment in AD and CAA patients. Therefore, in this study, we assessed the brain vasculome in a mouse model in order to identify cerebrovascular pathways that may be involved in AD and CAA vascular pathogenesis in the context of aging...

INTRODUCTION: About 80% of all non-traumatic intracerebral haemorrhage (ICH) are caused by the sporadic cerebral small vessel diseases deep perforator arteriopathy (DPA, also termed hypertensive arteriopathy or arteriolosclerosis) and cerebral amyloid angiopathy (CAA), though these frequently co-exist in older people. Contemporary neuroimaging (MRI and CT) detects an increasing spectrum of haemorrhagic and non-haemorrhagic imaging biomarkers of small vessel disease which may identify the underlying arteriopathies...

Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by amyloid β (Aβ) peptide deposition within the walls of medium to small-caliber blood vessels, cerebral microhemorrhage, and blood-brain barrier (BBB) leakage. It is commonly associated with late-stage Alzheimer's disease. BBB dysfunction is indicated as a pathological substrate for CAA progression with hyperpermeability, enhancing the extravasation of plasma components and inducing neuroinflammation, further worsening BBB injury and contributing to cognitive decline...

OBJECTIVE: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare manifestation related to CAA, thought to be more severe. We aimed to compare the clinical and radiological outcomes of CAA-ri and non-inflammatory CAA. MATERIALS AND METHODS: We retrospectively included all patients with CAA-ri from 13 French centers. We constituted a sex- and age-matched control cohort with non-inflammatory CAA and similar disease duration. Survival, autonomy and cognitive evolution were compared after logistic regression...

BACKGROUND AND OBJECTIVES: We present the case of a 67-year-old man who developed encephalopathy, headaches, and seizure activity after initiating treatment with the novel tyrosine kinase inhibitor, sitravatinib. METHODS: The patient was identified in routine clinical practice. RESULTS: Brain MRI revealed lobar microhemorrhages and bihemispheric vasogenic edema. The patient met the criteria for probable cerebral amyloid angiopathy-related inflammation (CAA-ri) and responded favorably to high-dose methylprednisolone...

CAA-ri is a reversible and rare encephalopathy that may manifest in patients with CAA. In this short article, we describe CT and MRI findings of CAA-ri in a 67-year-old man presented to emergency with sudden aphasia and acute cognitive dysfunction, underlining the pivotal role of neuroimaging in the diagnostic path.

No abstract text is available yet for this article.

Small-vessel disease (SVD), also known as microvascular endothelial dysfunction, is a disorder with negative consequences for various organs such as the heart and brain. Impaired dilatation and constriction of small vessels in the heart lead to reduced blood flow and ischemia independently of coronary artery disease (CAD) and are associated with major cardiac events. SVD is usually a silent form of subcortical vascular burden in the brain with various clinical manifestations, such as silent-lacunar-ischemic events and confluent white-matter hyperintensities...

A 59-year-old man with progressive cognitive decline and mood disturbances was admitted to the hospital. Brain magnetic resonance imaging revealed marked white matter hyperintensity (WMH) and widespread lobar cerebral microbleeds. Because he had untreated hypertension, we started antihypertensive treatment and found a significantly improved cognitive function and WMH regression. We diagnosed him with cerebral amyloid angiopathy (CAA) based on the modified Boston Criteria with the rare apolipoprotein (ApoE) ε2/ε4 genotype...

Neurovascular dysfunction, as an integral part of Alzheimer's disease, may have an important influence on the onset and progression of chronic neurodegenerative processes. The blood-brain barrier (BBB) pathway is one of the main pathways that mediates the clearance of amyloid-beta (Aβ) in the brain parenchyma. A large number of studies have shown that receptors and ATP-binding cassette transporters expressed on endothelial cells play an important role in Aβ transport across the BBB, but the specific mechanism is not clear...

No abstract text is available yet for this article.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare autoimmune encephalopathy of aging caused by an autoantibody immune response against Aβ protein deposited in the brain of older adults affected by cerebral amyloid angiopathy (CAA) and Alzheimer's disease pathology. Its most common clinical manifestations are (sub)acute-onset cognitive and behavioral abnormalities, focal deficits, seizures, and headaches. Brain magnetic resonance imaging shows characteristic extensive and confluent white matter hyperintensities and CAA features...