Giulia Abate

Nutrition and AGE-ing: Focusing on Alzheimer’s Disease

Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing (“AGE-ing”) is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss foods dual role as both source of bioactive nutrients and reservoir for potential toxic compounds—paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimers disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet.

Comparison of Extracellular and Intracellular Blood Compartments Highlights Redox Alterations in Alzheimer's and Mild Cognitive Impairment Patients

BACKGROUND Many studies suggest oxidative stress as an early feature of Alzheimers Disease (AD). However, evidence of established oxidative stress in AD peripheral cells is still inconclusive, possibly due to both, differences in the type of samples and the heterogeneity of oxidative markers used in different studies. OBJECTIVE The aim of this study was to evaluate blood-based redox alterations in Alzheimers Disease in order to identify a peculiar disease profile. METHOD To that purpose, we measured the activity of Superoxide Dismutase, Catalase and Glutathione Peroxidase both in the extracellular and the intracellular blood compartments of AD, MCI and control subjects. The amount of an open isoform of p53 protein (unfolded p53), resulting from oxidative modifications was also determined. RESULTS Decreased SOD, increased GPx activity and higher p53 open isoform were found in both AD and MCI plasma compared to controls. In blood peripheral mononuclear cells, SOD activity was also decreased in both AD and MCI, and unfolded p53 increased exquisitely in younger AD males compared to controls. CONCLUSION Overall, these data highlight the importance of considering both extracellular and intracellular compartments, in the determination of antioxidant enzyme activities as well as specific oxidation end-products, in order to identify peculiar blood-based redox alterations in AD pathology.

Characterization of the Antioxidant Effects of γ-Oryzanol: Involvement of the Nrf2 Pathway

γ-Oryzanol (ORY) is well known for its antioxidant potential. However, the mechanism by which ORY exerts its antioxidant effect is still unclear. In this paper, the antioxidant properties of ORY were investigated for its potential effects as a reactive oxygen and nitrogen species (ROS/RNS) scavenger and in activating antioxidant-promoting intracellular pathways utilizing the human embryonic kidney cells (HEK-293). The 24 h ORY exposure significantly prevented hydrogen peroxide- (H2O2-) induced ROS/RNS production at 3 h, and this effect was sustained for at least 24 h. ORY pretreatment also enhanced the activity of antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPX). Interestingly, ORY induced the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and upregulation of Nrf2-dependent defensive genes such as NAD(P)H quinone reductase (NQO1), heme oxygenase-1 (HO-1), and glutathione synthetase (GSS) at mRNA and protein levels in both basal condition and after H2O2 insult. Thus, this study suggested an intriguing effect of ORY in modulating the Nrf2 pathway, which is also involved in regulating longevity as well as age-related diseases.

Protein nitration profile of CD3+ lymphocytes from Alzheimer disease patients: Novel hints on immunosenescence and biomarker detection

&NA; Alzheimers disease (AD) is a progressive form of dementia characterized by increased production of amyloid‐&bgr; plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to decreased levels of CD3+ lymphocytes in peripheral blood in AD. Considering that oxidative stress, both in the brain and in the periphery, can influence the activation and differentiation of T‐cells, we investigated the 3‐nitrotyrosine (3‐NT) proteome of blood T‐cells derived from AD patients compared to non‐demented (ND) subjects by using a proteomic approach. 3‐NT is a formal protein oxidation and index of nitrosative stress. We identified ten proteins showing increasing levels of 3‐NT in CD3+ T‐cells from AD patients compared with ND subjects. These proteins are involved in energy metabolism, cytoskeletal structure, intracellular signaling, protein folding and turnover, and antioxidant response and provide new insights into the molecular mechanism that impact reduced T‐cell differentiation in AD. Our results highlight the role of peripheral oxidative stress in T‐cells related to immune‐senescence during AD pathology focusing on the specific targets of protein nitration that conceivably can be suitable to further therapies. Further, our data demonstrate common targets of protein nitration between the brain and the periphery, supporting their significance as disease biomarkers. Graphical abstract Figure. No caption available. HighlightsAD is characterized by modifications of the immune systems associated with reduced T‐cells activity.We identified increased protein nitration levels in T‐cells from AD patients compared to healthy subjects.The protein showing increased nitration are involved in pathways crucial to maintain neuronal homeostasis.Our data provide new insights into the molecular mechanisms that lead to reduced T‐cell differentiation in AD.The finding of common nitration targets between the brain and the periphery support their use in disease prediction.

FROM BLOOD-BASED REDOX PROFILE TO THE IDENTIFICATION OF A LEAD BIOMARKER FOR THE TIMELY DIAGNOSIS OF ALZHEIMER’S DISEASE

Nailfold capillary feature Category Multivariable* odds ratio (95% confidence interval) Unadjusted P value FDRAdjusted P value Mean tortuosity scorey 0 to <1 1.0 (ref) 1 to <2 3.4 (1.0, 12.2) .060 .083 2 14.1 (3.1, 63.9) .0006 .0036 Number of hemorrhages per 100 capillaries 0 to <1 1.0 (ref) 1 to <2 8.4 (1.9, 36.6) .0045 .014 2 4.4 (1.3, 14.9) .019 .037 Number of avascular zones 100 microns per 100 capillaries 0 to <1 1.0 (ref) 1 to <2 2.3 (0.6, 8.7) .23 .23 22 2.9 (0.9, 9.0) .069 .083

Enhanced Sensing of Interleukin 8 by Stripping Voltammetry: Carbon Nanotubes versus Fullerene

The ability to detect protein biomarkers at a sub-nanomolar level represents a pervasive challenge in order to bring a significant improvement in early diagnosis or progression of pato-physiological processes. To this aim, Screen Printed Electrochemical Sensors have been acquiring a predominant importance. The possibility to use them with different measurement techniques, and to customize their surface to improve the performance represent really attractive features. In this work, performances of two different carbon nanostructures in combination with Stripping Voltammetry were evaluated as tools to improve the detection of Interleukin 8, a cytokine that has pivotal roles in various inflammatory processes and considered as a universal biomarker. Commercially-available Carbon sensors were modified using Carbon Nanotubes and Spherical Fullerene through drop casting technique. Interleukin 8 was quantified using an indirect techniques based on silver stripping catalyzed using Alkaline Phosphatase. The nanostructured sensors showed better sensitivity with sub-nanomolar limit of detection: 0.39 ng/ml for carbon nanotubes and 0.61 ng/ml for fullerene compared to bare carbon electrodes. These modification method is promising for sensitive detection of protein biomarkers in several applications, including the monitoring of inflammatory processes.

Wireless Point-of-Care Platform With Screen-Printed Sensors for Biomarkers Detection

Measurement systems for early and reliable detection of degenerative diseases, such as Alzheimer’s disease (AD), are extremely important in clinical diagnosis. Among these, biochemical assays represent a commonly used method to distinguish patients from healthy population thanks to the sensitive recognition of specific biomarkers in biological fluids. In order to overcome actual limitations of these techniques in term of cost, standardization, and sensitivity, this study aimed to realize a low-cost highly sensitive portable point-of-care (PoC) testing system based on screen-printed electrochemical sensors. The development of the platform specifically included both the design of the sensing probe and the electronic circuit devoted to condition and acquires the transduced electric signal. The designed circuit was implemented in a printed circuit board and interfaced to a wireless system based on bluetooth data transmission in order to improve the portability of the proposed solution. Preliminary results were obtained by using controlled concentrations of electrolytic solutions and calibrating the sensors for antibodies and for a well-known protein (i.e., interleukin 8) quantified by anodic stripping voltammetry (ASV). Findings from ASV measurements showed a sensitivity of

A NEW PUTATIVE EARLY BIOMARKER FOR A BLOOD-BASED TIMELY DIAGNOSIS FOR ALZHEIMER’S DISEASE

38~\mu \text{A}

AN OPEN ISOFORM OF P53 AS AN EARLY BIOMARKER OF BLOOD REDOX ALTERATIONS IN ALZHEIMER’S DISEASE: DEVELOPMENT OF AN EASY AND REPRODUCIBLE ASSAY

/(ng/ml) with a tested range from 1.25 to 20 ng/ml, with a limit of detection of 2 ng/ml. Further investigation will include the validation of this PoC device by testing the concentration of a specific p53 protein isoform, which was recently identified to early correlate to AD development.

Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer’s Disease and Mild Cognitive Impairment Patients

2-Aminoadipic acid Amines TG(51:3) Lipids: Triglycerides 3-Hydroxyisovaleric acid Organic acids Tyrosine Amines TG(54:6) Lipids: Triglycerides TG(50:4) Lipids: Triglycerides S-3-Hydroxyisobutyric acid Organic acids TG(56:8) Lipids: Triglycerides Methyldopa Amines 8-iso-PGF2a (15-F2t-IsoP) Oxidative stress: Isoprostane TG(48:3) Lipids: Triglycerides O-Acetylserine Amines TG(48:2) Lipids: Triglycerides Methylmalonic acid Organic acids TG(46:2) Lipids: Triglycerides Valine Amines TG(50:3) Lipids: Triglycerides TG(52:4) Lipids: Triglycerides TG(52:5) Lipids: Triglycerides TG(56:7) Lipids: Triglycerides TG(48:0) Lipids: Triglycerides Ornithine Amines SM(d18:1/23:0) Lipids: Sphingomyelins SM(d18:1/20:1) Lipids: Sphingomyelins TG(48:1) Lipids: Triglycerides TG(58:10) Lipids: Triglycerides Poster Presentations: Tuesday, July 18, 2017 P1025