Amyloid-Related Imaging Abnormalities (ARIA) in Clinical Trials of Gantenerumab in Early Alzheimer Disease.

Importance: Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae.

Objectives: To describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E).

Design, Setting, And Participants: Secondary data collection from the GRADUATE I/II phase 3 randomized, double-blind, placebo-controlled, 116-week parallel-group studies and their open-label extensions, including PostGraduate, with up to 210 (mean, 125) weeks of total gantenerumab treatment were conducted between 2018 and 2023.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy.

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.

In silico exploration of amyloid-related imaging abnormalities in the gantenerumab open-label extension trials using a semi-mechanistic model.

Introduction: Amyloid-related imaging abnormalities with edema/effusion (ARIA-E) are commonly observed with anti-amyloid therapies in Alzheimer's disease. We developed a semi-mechanistic, in silico model to understand the time course of ARIA-E and its dose dependency.

Methods: Dynamic and statistical analyses of data from 112 individuals that experienced ARIA-E in the open-label extension of SCarlet RoAD (a study of gantenerumab in participants with prodromal Alzheimer's disease) and Marguerite RoAD (as study of Gantenerumab in participants with mild Alzheimer's disease) studies were used for model building.

Quantitative proteomic profiling of white matter in cases of cerebral amyloid angiopathy reveals upregulation of extracellular matrix proteins and clusterin.

Cerebral amyloid angiopathy (CAA) is the accumulation of amyloid beta (Aβ) in the walls of cerebral arterioles, arteries and capillaries. Changes in the white matter in CAA are observed as hyperintensities and dilated perivascular spaces on MRI suggesting impairment of fluid drainage but the pathophysiology behind these changes is poorly understood. We tested the hypothesis that proteins associated with clearance of Aβ peptides are upregulated in the white matter in cases of CAA.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA): Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease-Opportunities for Therapy.

Two of the key functions of arteries in the brain are (1) the well-recognized supply of blood via the vascular lumen and (2) the emerging role for the arterial walls as routes for the elimination of interstitial fluid (ISF) and soluble metabolites, such as amyloid beta (Aβ), from the brain and retina. As the brain and retina possess no conventional lymphatic vessels, fluid drainage toward peripheral lymph nodes is mediated via transport along basement membranes in the walls of capillaries and arteries that form the intramural peri-arterial drainage (IPAD) system. IPAD tends to fail as arteries age but the mechanisms underlying the failure are unclear.

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia.

White matter hyperintensities (WMH) occur in association with dementia but the aetiology is unclear. Here we test the hypothesis that there is a combination of impaired elimination of interstitial fluid from the white matter together with a degree of hypoxia in WMH. One of the mechanisms for the elimination of amyloid-β (Aβ) from the brain is along the basement membranes in the walls of capillaries and arteries (Intramural Peri-Arterial Drainage - IPAD).

Vasomotion Drives Periarterial Drainage of Aβ from the Brain.

In this issue of Neuron, van Veluw et al. (2020) show that elimination of solutes from the brain along arterial walls is driven by low-frequency arteriolar oscillations and suggest that age-related reduction of this vasomotion may contribute to impaired clearance of Aβ.

Cerebrovascular Smooth Muscle Cells as the Drivers of Intramural Periarterial Drainage of the Brain.

The human brain is the organ with the highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that the basement membranes of cerebral capillaries and arteries represent the lymphatic pathways of the brain along which intramural periarterial drainage (IPAD) of soluble metabolites occurs. Failure of IPAD could explain the vascular deposition of the amyloid-beta protein as cerebral amyloid angiopathy (CAA), which is a key pathological feature of Alzheimer's disease.

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Aβ). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer's disease.

[The possibility of a multiresolution wavelet analysis for detecting the P300 event related potential].

Unlabelled: The main objective is to high-light the P300 potential on certain electroencephalographic signals. P300 occurs at a relatively well defined time in relation to a stimulus and it represents a signal with a specified band frequency.

Method: The electroencephalographic (EEG) was recorded with 4 wet electrodes by means of g.

Computer simulations of in vitro morphogenesis.

One of the most important challenges of contemporary biology is understanding how cells assemble into tissues. The complexity of morphogenesis calls for computational tools able to identify the dominant mechanisms involved in shaping tissues. This narrative review presents individual-based computational models that proved useful in simulating phenomena of interest in tissue engineering (TE), a research field that aims to create tissue replacements in the laboratory.

Perioperative management of hemostasis for surgery of benign hepatic adenomas in patients with glycogen storage disease type ia.

The development of hepatocellular adenomas in the liver of patients with glycogen storage disease type I is a well-known complication of the disease. Surgical procedures and perioperative managements described so far have reported persistent and important morbidity. We report here a series of six patients (three males and three females) who underwent hepatic resection, and we propose a new hemostatic management protocol comprising glucose infusion, corticosteroids, desmopressin, and antifibrinolytic drugs, used to prevent efficaciously hepatic hemorrhage due to glycogen storage disease (GSD) platelet dysfunction.

[Anaphylactic shock from succinylcholine, complicated by a rhabdomyolysis].

A young woman, with a contact dermatitis to nickel, experienced a life threatening anaphylaxis after induction of general anaesthesia for an emergency curettage. Hypersensitivity reaction involving IgE antibodies against succinylcholine was proven by positive skin test and radioimmunoassay detection of antibodies against succinylcholine and quaternary ammonium. After restoration of haemodynamics in a few hours, the patient had rhabdomyolysis predominant at lower left leg, which required a fasciotomy.