Immunotherapies in Alzheimer’s disease: Too much, too little, too late or off-target?

Abstract Years of research have highlighted the importance of the immune system in Alzheimer’s disease (AD), a system that, if manipulated during strategic time windows, could potentially be tackled to treat this disorder. However, to minimize adverse effects, it is essential to first grasp which exact aspect of it may be targeted. Several clues have been collected over the years regarding specific immune players strongly modulated during different stages of AD progression. However, the inherent complexity of the immune system as well as conflicting data make it quite challenging to pinpoint a specific immune target in AD. In this review, we discuss immune-related abnormalities observed in the periphery as well as in the brain of AD patients, in relation to known risk factors of AD such as genetics, type-2 diabetes or obesity, aging, physical inactivity and hypertension. Although not investigated yet in clinical trials, C5 complement system component, CD40/CD40L interactions and the CXCR2 pathway are altered in AD patients and may represent potential therapeutic targets. Immunotherapies tested in a clinical context, those aiming to attenuate the innate immune response and those used to facilitate the removal of pathological proteins, are further discussed to try and understand the causes of the limited success reached. The prevailing eagerness to move basic research data to clinic should not overshadow the fact that a careful preclinical characterization of a d...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Metabolic syndrome, characterized by central obesity, hypertension, and hyperlipidemia, increases the morbidity and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that hepatic fatty acid accumulation can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria ar...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Purpose of review Through its direct adverse effects on the kidney and via associated intermediate disease states like type 2 diabetes and hypertension, obese has arguably become the master risk factor for chronic kidney disease (CKD). The purpose of this review is to critically evaluate bariatric surgery, which is the most effective weight reduction strategy available, as a renoprotective strategy. Recent findings Recent randomized studies confirm that bariatric surgery is effective at improving or even remitting major CKD risk factors such as type 2 diabetes and hypertension. In addition, observational studies perfo...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: DIAGNOSTICS AND TECHNIQUES: Edited by Maarten W. Taal Source Type: research
Authors: Gao RY, Hsu BG, Wu DA, Hou JS, Chen MC Abstract Background: Fibroblast growth factor 21 (FGF21) acts as a potent metabolic regulator. Serum FGF21 levels were significantly higher in obesity and type 2 diabetes mellitus (T2DM) populations. The aim of this study was to evaluate the relationship between serum FGF21 levels and metabolic syndrome (MetS) in T2DM patients. Methods: Fasting blood samples were obtained from 126 T2DM patients. MetS and its components were defined according to the diagnostic criteria from the International Diabetes Federation. Serum FGF21 concentrations were measured using a comm...
Source: International Journal of Endocrinology - Category: Endocrinology Tags: Int J Endocrinol Source Type: research
The conditions of human life began to improve with the Enlightenment of the 18th century, and we are better off now by many measures: food access, health, lifespan, and so on. But it hasn’t been an unbroken line of advancement. In the last three decades, U.S. death rates have risen steeply from suicide and compulsive consumption of alcohol and drugs, which Princeton University professors Anne Case and Angus Deaton famously termed “deaths of despair.” Exceeding these deaths of despair by tenfold are rising deaths from type 2 diabetes, hypertension, and cardiovascular disease—caused significantly by c...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized Addiction diabetes Mental Health/Psychology neuroscience Source Type: news
Conclusions:Higher levels of serum chromium were observed in smokers, whereas lower levels were found to be present in patients with T2D and patients with prediabetes. In addition, serum chromium level may not be affected by hypertension, overweight and obesity, and family history of diabetes.Keywords:Obesity, overweight, serum chromium, smokers, type 2 diabetes, prediabetes, hypertension
Source: International Journal of Preventive Medicine - Category: International Medicine & Public Health Source Type: research
Authors: Selthofer-Relatić K, Kibel A, Delić-Brkljačić D, Bošnjak I Abstract Obesity is a risk factor for cardiometabolic and vascular diseases like arterial hypertension, diabetes mellitus type 2, dyslipidaemia, and atherosclerosis. A special role in obesity-related syndromes is played by cardiac visceral obesity, which includes epicardial adipose tissue and intramyocardial fat, leading to cardiac steatosis; hypertensive heart disease; atherosclerosis of epicardial coronary artery disease; and ischemic cardiomyopathy, cardiac microcirculatory dysfunction, diabetic cardiomyopathy, and atrial fibrillation...
Source: Journal of Obesity - Category: Eating Disorders & Weight Management Tags: J Obes Source Type: research
Obesity causes and exacerbates many disease processes and affects every organ system. Thus it is not surprising that clinical providers are often overwhelmed with the multitude of symptomatology upon initial presentation in patients with obesity. However, despite a “complicated medical history,” a systematic, organized approach in obesity medicine utilizes a personalized-tailored treatment strategy coupled with understanding of the disease state, presence of comorbidities, contraindications, side effects, and patient preferences. Here, we present the case of a young patient with Class 3b severe obesity, several...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
The objective of this review is to show an overview to know the main UT produced in end-stage renal disease patients, and how prebiotics and probiotics intervention acts as a helpful tool in CKD treatment.
Source: International Urology and Nephrology - Category: Urology & Nephrology Source Type: research
Obesity has reached the pandemic level. It has dramatically increased over recent decades and is now one of the most important public health problems facing both urban and rural areas.1 Among youths, the worldwide prevalence of overweight and obesity has risen by 47.1% since 1980.2 Pediatric obesity is associated with comorbidities affecting the cardiovascular (CV), pulmonary, endocrine, gastrointestinal, and musculoskeletal systems,3 and it seems to be the predominant cause of conditions such as hypertension, type 2 diabetes mellitus, dyslipidemia, insulin resistance, inflammation, and steatohepatitis.
Source: Mayo Clinic Proceedings - Category: Internal Medicine Authors: Tags: Editorial Source Type: research
ConclusionConsensus has been reached for a variety of statements regarding the management of several T2D profiles. Achieving a more homogeneous management of complex patients with T2D may require further evidence and a better understanding of the key drivers for treatment choice.FundingLogistic support was provided by ESTEVE Pharmaceuticals S.A Spain.
Source: Diabetes Therapy - Category: Endocrinology Source Type: research
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