Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics.

Excess accumulation and aggregation of toxic soluble and insoluble amyloid-ß species in the brain are a major hallmark of Alzheimer's disease. Randomized clinical trials show reduced brain amyloid-ß deposits using monoclonal antibodies that target amyloid-ß and have identified MRI signal abnormalities called amyloid-related imaging abnormalities (ARIA) as possible spontaneous or treatment-related adverse events. This review provides a comprehensive state-of-the-art conceptual review of radiological features, clinical detection and classification challenges, pathophysiology, underlying biological mechanism(s) and risk factors/predictors associated with ARIA. We summarize the existing literature and current lines of evidence with ARIA-oedema/effusion (ARIA-E) and ARIA-haemosiderosis/microhaemorrhages (ARIA-H) seen across anti-amyloid clinical trials and therapeutic development. Both forms of ARIA may occur, often early, during anti-amyloid-ß monoclonal antibody treatment. Across randomized controlled trials, most ARIA cases were asymptomatic. Symptomatic ARIA-E cases often occurred at higher doses and resolved within 3-4 months or upon treatment cessation. Apolipoprotein E haplotype and treatment dosage are major risk factors for ARIA-E and ARIA-H. Presence of any microhaemorrhage on baseline MRI increases the risk of ARIA. ARIA shares many clinical, biological and pathophysiological features with Alzheimer's disease and cerebral amyloid angiopathy. There is a great need to conceptually link the evident synergistic interplay associated with such underlying conditions to allow clinicians and researchers to further understand, deliberate and investigate on the combined effects of these multiple pathophysiological processes. Moreover, this review article aims to better assist clinicians in detection (either observed via symptoms or visually on MRI), management based on appropriate use recommendations, and general preparedness and awareness when ARIA are observed as well as researchers in the fundamental understanding of the various antibodies in development and their associated risks of ARIA. To facilitate ARIA detection in clinical trials and clinical practice, we recommend the implementation of standardized MRI protocols and rigorous reporting standards. With the availability of approved amyloid-ß therapies in the clinic, standardized and rigorous clinical and radiological monitoring and management protocols are required to effectively detect, monitor, and manage ARIA in real-world clinical settings.

COVID-19: Testing Landscape Post-Infection, -Vaccination, and Future Perspectives.

On March 11, 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak a global pandemic. Although molecular testing remains the gold standard for COVID-19 diagnosis, serological testing enables the evaluation of the immune response to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and vaccination, and can be used to assess community viral spread. This review summarizes and analyzes the current landscape of SARS-CoV-2 testing in the United States and includes guidance on both when and why it is important to use direct pathogen detection and/or serological testing. The usefulness of monitoring humoral and cellular immune responses in infected and vaccinated patients is also addressed. Finally, this review considers current challenges, future perspectives for SARS-CoV-2 testing, and how diagnostics are being adapted as the virus evolves.

The AT(N) system for describing biological changes in Alzheimer's disease: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of an article published in Nature Reviews Neurology. It explains how Alzheimer's disease is diagnosed. It also looks at whether a newer way to assess people with Alzheimer's disease could help improve how the condition is diagnosed, monitored, and treated. WHY IS THIS IMPORTANT?: Alzheimer's disease is a long-term progressive brain disease that leads to difficulties with thinking and memory. It is a progressive condition, which means it gets worse over time. Biological changes occur in the brain of people with Alzheimer's disease. This includes a build-up of toxic protein clusters called amyloid plaques and tau tangles, gradual damage to the brain cells (neurodegeneration), and brain shrinkage due to loss of neurons. It is often due to multiple factors and doctors usually diagnose Alzheimer's disease by looking at a person's symptoms and ruling out other causes of dementia. However, research shows that people diagnosed in this way do not always have the biological changes in the brain that are related to Alzheimer's disease. This means that some people may be misdiagnosed. Additionally, there may be a delay in the appearance of Alzheimer's symptoms, by which point changes in the brain may be severe. For example, people with Alzheimer's disease show biological changes in the brain, years before symptoms appear. WHAT ARE THE KEY TAKEAWAYS?: An assessment of biological changes in the brain, by measuring substances that indicate disease progress (biomarkers), may offer a fuller picture of a person's Alzheimer's disease, how advanced it is, and which treatments are likely to work best. A recently developed classification scheme known as the AT(N) system provides a way to assess and describe the biological changes in amyloid (A), tau (T), and neurodegeneration (N) that occur in people with Alzheimer's disease. The goal is to include biomarker testing in clinical practice to help physicians and practitioners diagnose, monitor, and treat people with Alzheimer's disease more effectively. The AT(N) system is being used for various purposes in clinical studies, and has the potential to assist physicians and practitioners in early detection, accurate diagnosis, staging, and treatment selection for people with Alzheimer's disease.

The use of lumbar puncture and safety recommendations in Alzheimer's disease: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of an article published in Alzheimer's & Dementia. It looks at a type of test called a lumbar puncture (also known as spinal tap) used in people suspected of having Alzheimer's disease or some other form of dementia. This summary focuses on how to do a lumbar puncture safely. WHY IS THIS IMPORTANT?: Alzheimer's disease is a progressive condition, which means it gets worse over time. This leads to difficulties with thinking and memory. People with Alzheimer's disease show a build up of proteins called amyloid-ß and tau in the brain. This is followed by a gradual loss of brain cells and brain function. The changes in the brain are thought to occur years before symptoms appear. Lumbar puncture is a medical procedure during which samples of cerebrospinal fluid are collected. In Alzheimer's disease, it is used to examine cerebrospinal fluid biomarkers that can help diagnose disease. Lumbar puncture is traditionally considered as a painful and invasive procedure with frequent side effects. However, multiple studies indicate that a lumbar puncture can be performed safely. Side effects are typically mild and do not require specialist intervention. WHAT ARE THE KEY TAKEAWAYS?: Despite the low risk of serious complications associated with a lumbar puncture, physicians and their patients may be reluctant to recommend or undergo this procedure. Patient education, specialist training, as well as new methods concerning patient safety are important factors to support the widespread use of lumbar puncture in Alzheimer's disease.

Amyloid-related imaging abnormalities (ARIA) and their radiological, biological and clinical characteristics: a plain language summary.

What is this summary about? This is a plain language summary of an article published in the journal Brain. People with Alzheimer's disease may receive treatments that target amyloid-ß ­ a protein in the brain that is one of the key characteristics of Alzheimer's disease when it is present in higher levels than normal. This article is about amyloid-related imaging abnormalities (ARIA), which can be adverse events for people with Alzheimer's disease receiving antibody treatments targeting amyloid-ß (known as anti­amyloid-ß antibody treatments). This article also discusses ways to identify and manage ARIA.ARIA are adverse events that happen due to amyloid-ß buildup in the brain or following treatments targeting amyloid-ß. ARIA are identified on MRI scans as swelling or bleeding in the brain, and people with ARIA do not typically have symptoms. In rare cases, ARIA can cause serious symptoms or lead to disability.What are the key takeaways? There are two types of ARIA: ARIA-E (swelling in the brain) and ARIA-H (bleeding in the brain).Presence of an APOE ε4 gene variant and exposure to anti­amyloid-ß antibody treatments are major risk factors for ARIA.With the recent availability in the clinic of antibody treatments targeting amyloid-ß, increased awareness is needed to identify, monitor and manage ARIA effectively.What were the main conclusions reported by the researchers? Uniform detection, monitoring and management of ARIA are essential in patients receiving antibody treatments targeting amyloid-ß. To increase ARIA detection in clinical trials and clinical practice, the authors recommend the implementation of uniform imaging protocols and rigorous reporting standards.

Examination of the Addictive and Behavioral Properties of Fatty Acid-Binding Protein Inhibitor SBFI26.

The therapeutic properties of cannabinoids have been well demonstrated but are overshadowed by such adverse effects as cognitive and motor dysfunction, as well as their potential for addiction. Recent research on the natural lipid ligands of cannabinoid receptors, also known as endocannabinoids, has shed light on the mechanisms of intracellular transport of the endocannabinoid anandamide by fatty acid-binding proteins (FABPs) and subsequent catabolism by fatty acid amide hydrolase. These findings facilitated the recent development of SBFI26, a pharmacological inhibitor of epidermal- and brain-specific FABP5 and FABP7, which effectively increases anandamide signaling. The goal of this study was to examine this compound for any possible rewarding and addictive properties as well as effects on locomotor activity, working/recognition memory, and propensity for sociability and preference for social novelty (SN) given its recently reported anti-inflammatory and analgesic properties. Male C57BL mice were split into four treatment groups and conditioned with 5.0, 20.0, 40.0 mg/kg SBFI26, or vehicle during a conditioned place preference (CPP) paradigm. Following CPP, mice underwent a battery of behavioral tests [open field, novel object recognition (NOR), social interaction (SI), and SN] paired with acute SBFI26 administration. Results showed that SBFI26 did not produce CPP or conditioned place aversion regardless of dose and did not induce any differences in locomotor and exploratory activity during CPP- or SBFI26-paired open field activity. We also observed no differences between treatment groups in NOR, SI, and SN. In conclusion, as SBFI26 was shown previously by our group to have significant analgesic and anti-inflammatory properties, here we show that it does not pose a risk of dependence or motor and cognitive impairment under the conditions tested.