Differences between plasma and CSF p-tau181 and p-tau231 in early Alzheimer s disease

Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer s disease pathology. In this cross-sectional study incuding ninety-one subjects, plasma p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD, with similar levels than those of CSF. Plasma p-tau231 and p-tau181 were strongly related to CSF tau and amyloid and exhibited a high accuracy, close to CSF p-tau231 and p-tau181, to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings.

Mitochondrial Dysfunction as a Causative Factor in Alzheimer’s Disease-Spectrum Disorders: Lymphocytes as a Window to the Brain

: Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will further increase with longer life expectancy. The AD brain is marked by severe neurodegeneration, such as the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems, especially in the hip- pocampus and cerebral cortex. Recent findings highlight the important role of mitochondrial dys- function and increased oxidative stress in the pathophysiology of late-onset Alzheimer’s disease (LOAD). These alterations are not only observed in the brain of AD patients but also in the periph- ery. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and mitochondrial dysfunction as peripheral markers for the detection of AD in blood cells e.g. lymphocytes. We evaluate recent findings regarding impaired mitochondrial function comprising mitochondrial respiration, reduced complex activities of the respiratory chain and altered Mitochon- drial Membrane Potential (MMP) in lymphocytes as well as in neurons. Finally, we will question whether these mitochondrial parameters might be suitable as an early peripheral marker for the de- tection of LOAD but also for the transitional stage between normal aging and Dementia, “Mild Cognitive Impairment” (MCI).

New Molecular Targets for Antidepressant Drugs

Major depressive disorder (MDD) is a common and severe mental disorder that is usually recurrent and has a high risk of suicide. This disorder manifests not only with psychological symptoms but also multiple changes throughout the body, including increased risks of obesity, diabetes, and cardiovascular disease. Peripheral markers of oxidative stress and inflammation are elevated. MDD is therefore best described as a multisystem whole-body disease. Pharmacological treatment with antidepressants usually requires several weeks before the desired effects manifest. Previous theories of depression, such as the monoamine or neurogenesis hypotheses, do not explain these characteristics well. In recent years, new mechanisms of action have been discovered for long-standing antidepressants that also shed new light on depression, including the sphingolipid system and the receptor for brain-derived neurotrophic factor (BDNF).

Peripheral Oxidation Markers in Down Syndrome Patients: The Better and the Worse

Oxidative stress plays an important role in Down syndrome (DS) pathology since the gene dose effect leads to abnormal levels of certain enzymes and metabolites. In this review, we focused on relatively easy-to-obtain, peripheral markers of oxidative stress and inflammation, in order to compare the levels of these markers in DS patients and chromosomally healthy persons. Studies taking into account age- and sex-matched control groups were of particular interest in this context. We analyzed the factors that influence the levels of said markers in both groups (i.e., the usefulness of the markers), including the age of DS patients, occurrence of regular trisomy 21 or mosaicism, physical activity of patients, and the onset of Alzheimer’s disease in DS. This paper was conceived as a handbook—to help for selecting suitable, easy-to-obtain markers for monitoring of the health status of DS patients (e.g., in nutritional studies and during dietary supplementation).

Effect of liraglutide on neural and peripheral markers of metabolic function during antipsychotic treatment in rats

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that prevents metabolic side effects of the antipsychotic drugs (APDs) olanzapine and clozapine through unknown mechanisms. Aim: This study aimed to investigate the effect of chronic APD and liraglutide co-treatment on key neural and peripheral metabolic signals, and acute liraglutide co-treatment on clozapine-induced hyperglycaemia. Methods: In study 1, rats were administered olanzapine (2 mg/kg), clozapine (12 mg/kg), liraglutide (0.2 mg/kg), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle for six weeks. Feeding efficiency was examined weekly. Examination of brain tissue (dorsal vagal complex (DVC) and mediobasal hypothalamus (MBH)), plasma metabolic hormones and peripheral (liver and kidney) cellular metabolism and oxidative stress was conducted. In study 2, rats were administered a single dose of clozapine (12 mg/kg), liraglutide (0.4 mg/kg), clozapine + liraglutide co-treatment or vehicle. Glucose tolerance and plasma hormone levels were assessed. Results: Liraglutide co-treatment prevented the time-dependent increase in feeding efficiency caused by olanzapine, which plateaued by six weeks. There was no effect of chronic treatment on melanocortinergic, GABAergic, glutamatergic or endocannabionoid markers in the MBH or DVC. Peripheral hormones and cellular metabolic markers were unaltered by chronic APD treatment. Acute liraglutide co-treatment was unable to prevent clozapine-induced hyperglycaemia, but it did alter catecholamine levels. Conclusion: The unexpected lack of change to central and peripheral markers following chronic treatment, despite the presence of weight gain, may reflect adaptive mechanisms. Further studies examining alterations across different time points are required to continue to elucidate the mechanisms underlying the benefits of liraglutide on APD-induced metabolic side effects.

Relationship between heat storage and parameters of thermotolerance and fatigue in exertional-heat stress

Background/Aim. The risk assessment of heat illness and fatigue development is very important in military services. the aim of our study was to investigate the relationship between heat storage and various psychophysiological parameters of heat stress, as well as potential peripheral markers of fatigue in soldiers performing exertional heat stress test. Methods. 15 young, healthy and unacclimatized men underwent exertional heat stress test (EHST) with submaximal work load in warm conditions (WBGT 29 ?C) in climatic chamber. Every 5 minutes following parameters of thermotolerance were measured or calculated: core temperature (Tc), mean skin (Tsk) and body temperature (Tb), heart rate (HR), heat storage (HS), physiological strain index (PSI), as well as peripheral markers of fatigue (blood concentrations of ammonia, urea nitrogen (BUN), lactate dehydrogenase (LDH), cortisol and prolactin) and subjective parameters: thermal sensation (TS) and rate of perceived exertion (RPE). Results. Tolerance time varied from 45-75 minutes (63?7,7 min). Average values of Tc, Tb, and HR constantly increased during EHST, while Tsk after 10 minutes reached the plateau. Concentrations of all investigated peripheral markers of fatigue were significantly higher after EHST compared to baseline levels (31,47?7,29 vs. 11,8?1,11 ?mol/l for ammonia; 5,92?0,73 vs. 4,69?0,74 mmol/l for BUN, 187,27?28,49 vs.152,73?23,39 U/l for LDH, 743,43?206,19 vs. 558,79?113,34 mmol/l for cortisol and 418,08?157,14 vs. 138,79?92,83 ?IU/mL for prolactin). Conclusions. This study demonstrates the relationship between heat storage and Tc, HR, TS and RPE, but also with PSI. Concentrations of cortisol and especially prolactin showed significant correlation with parameters of thermotolerance.