BACE-1 and ADAM-10 as Potential Peripheral Biomarkers for Alzheimer's Disease.

Amyloid beta (Aβ) dyshomeostasis is considered the main biological aberration in Alzheimer's Disease (AD) pathology. The interplay between Aβ formation and clearance is predominantly modulated by a disintegrin and a metalloproteinase 10 (ADAM10, α-secretase) and β-site APP Cleaving Enzyme 1 (BACE1), the two pivotal enzymes in both non-amyloidogenic/amyloidogenic and amyloidolytic pathways. Emerging evidence suggests that aberrations in ADAM10 and BACE1 expression, activity, and function in the brain of AD patients also manifest in peripheral fluids, suggesting their potential as blood-based biomarkers for AD diagnosis.

PON1 and PON3 in Alzheimer's Disease: Similar Functions but Different Roles.

Paraoxonase 1 (PON1) and Paraoxonase 3 (PON3) are enzymes located on the surface of high-density lipoprotein (HDL) and share similar antioxidant properties, possibly modulated by other proteins such as Myeloperoxidase (MPO), which drives the shift from functional to dysfunctional HDL. PON1 has been extensively studied in relation to Alzheimer's Disease (AD), but the role of PON3 remains unknown. To fill this knowledge gap, the study analyzed PON3 protein levels and PON1-arylesterase activity in 99 AD patients, 100 patients with mild cognitive impairment (MCI), and 79 cognitively normal controls.

Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the two major neurodegenerative diseases causing dementia. Due to similar clinical phenotypes, differential diagnosis is challenging without specific biomarkers. Beta-site Amyloid Precursor Protein cleaving enzyme 1 (BACE1) is a β-secretase pivotal in AD pathogenesis.

Neutrophil-Lymphocytes Ratio as Potential Early Marker for Alzheimer's Disease.

Background: Neutrophil-lymphocyte ratio (NLR) is a noninvasive, inexpensive, and easily applicable marker of inflammation. Since immune dysregulation leading to inflammation is regarded as a hallmark of dementia, in particular Alzheimer's disease (AD), we decided to investigate the potentials of NLR as a diagnostic and predictive biomarker in this clinical setting.

Materials And Methods: NLR was measured in the blood of patients with AD ( = 103), amnestic type mild cognitive impairment (aMCI,  = 212), vascular dementia (VAD,  = 34), and cognitively healthy Controls ( = 61).

Active myeloperoxidase: a promising biomarker to differentiate "acute" and "low-grade" peri-prosthetic joint infections from aseptic failures.

Introduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy.

Transcriptomics Studies Reveal Functions of Transglutaminase 2 in Breast Cancer Cells Using Membrane Permeable and Impermeable Inhibitors.

Transglutaminase 2 (TG2) performs many functions both under physiological and pathological conditions. In cancer, its expression is associated with aggressiveness, propensity to epithelial-mesenchymal transition, and metastasis. Since TG2 performs key functions both outside and inside the cell, using inhibitors with different membrane permeability we analyzed the changes in the transcriptome induced in two triple-negative cell lines (MDA-MB-436 and MDA-MB-231) with aggressive features.

Variability in Alzheimer's disease mortality from European vital statistics, 2012-2020.

Objective: Data regarding the trends in Alzheimer's disease (AD) mortality in the modern European Union (EU-27) member states are lacking. We assess the sex- and age-specific trends in AD mortality in the EU-27 member states between years 2012 and 2020.

Methods: Data on cause-specific deaths and population numbers by sex for each country of the EU-27 were retrieved through publicly available European Statistical Office (EUROSTAT) dataset from 2012 to 2020.

Acetyl-cholinesterase-inhibitors reconsidered. A narrative review of post-marketing studies on Alzheimer's disease.

The real efficacy of Acetyl-cholinesterase-inhibitors (AChEI) has been questioned. In this narrative review we evaluated their effect on cognitive decline, measured by Mini Mental State Examination (MMSE), and on total mortality rates in patients with Alzheimer's disease (AD) recruited into post-marketing open/non-randomized/retrospective studies. In AD patients treated with AChEI, the mean MMSE loss ranged from 0.

Signature of paraoxonases in the altered redox homeostasis in Alzheimer's disease.

Paraoxonase (PON) enzymes (PON1, PON2 and PON3) exert antioxidant properties through arylesterase, lactonase and paraoxonase activities. Increasing findings suggested their potential involvement, particularly PON1 and PON2, in Alzheimer's disease (AD), a neurodegenerative pathology characterized by early oxidative stress. Specifically, decreased serum PON1-arylesterase and lactonase activities seem to be associated with an increased brain oxidative damage in early AD, leading to hypothesize that PON activity alterations might be an early event in AD.

Serum zonulin levels are increased in Alzheimer's disease but not in vascular dementia.

Background: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood-brain barrier (BBB) by regulating tight junction molecular assembly.

Aim: Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI).

Methods: We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls.

Paraoxonase 1 activity in patients with Alzheimer disease: Systematic review and meta-analysis.

Cumulating evidence links environmental toxicants, such as organophosphate (OP) pesticides, to the pathogenesis of Alzheimer's disease (AD). The calcium-dependent Paraoxonase 1 (PON1) can neutralize these toxicants with good catalytic efficiency, thus protecting from OP-induced biological damage. Although different previous studies have already partially described an association between PON1 activity and AD, this intriguing relationship has not yet been comprehensively examined.

Frontier on Alzheimer's Disease.

Although substantial progress has been made in the last two decades, there are still important unfilled gaps in the understanding of the pathomechanism of Alzheimer's disease (AD) [...

Lipoprotein-Associated Phospholipase A2 Activity as Potential Biomarker of Vascular Dementia.

A wealth of evidence suggests that Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a relevant role in atherogenesis and inflammation, which in turn are associated with the risk of developing dementia. The aim of this study was to evaluate whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia. Serum Lp-PLA2 activity was assessed in older patients with mild cognitive impairment (MCI, = 166; median clinical follow-up = 29 months), Late-Onset Alzheimer's disease (LOAD, = 176), vascular dementia (VAD, = 43), dementia characterized by an overlap between LOAD and VAD (AD-VAD MIXED dementia) ( = 136), other dementia subtypes ( = 45), and cognitively normal controls ( = 151).

A Calcium- and GTP-Dependent Transglutaminase in .

While human and animal leishmaniasis affect several millions of people worldwide, is the species responsible for visceral leishmaniasis in Europe, Middle East, and America. Antileishmanial drugs present issues associated with drug toxicity and increasing parasite resistance. Therefore, the study of this parasite with a focus on new potential drug targets is extremely useful.

Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides.

Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective.

A Nutraceutical Compound Containing a Low Dose of Monacolin K, Polymethoxyflavones, Phenolic Acids, Flavonoids, and Hydroxytyrosol Improves HDL Functionality.

Background: In earlier studies, it has been observed that 8-week treatment with a novel nutraceutical compound (NC) containing low monacolin K dose, polymethoxyflavones, phenolic acids, flavonoids, and hydroxytyrosol improves lipid profile and endothelial function and reduces the level of oxidized low-density lipoprotein (oxLDL). We hypothesize that this effect might be, at least in part, explained by positive modulation exerted by the NC on the atheroprotective function of high-density lipoprotein (HDL).

Aim: This study aimed to evaluate whether the NC could influence determinants of HDL function.

Age, Sex, Hypertension and HDL-C Alter Serum BACE1 Activity in Cognitively Normal Subjects: Implications for Alzheimer's Disease.

Background: Increasing evidence indicates that β-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs.

Objectives: To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity.

Predictive Factors of Surgical Site Infection in Prosthetic Joint Surgery: A Prospective Study on 760 Arthroplasties.

Purpose: The success of total joint arthroplasty (TJA) has led to consistent growth in the use of arthroplasty in progressively younger patients. However, more than 10 percent of patients require revision surgery due to implant failure caused by aseptic or septic inflammation. Among the latter, surgical site infection (SSI) represents one of the worst complications of TJA, potentially resulting in the removal of the prosthesis.

Fermentation of Berries with Reduces Oxidative Stress in Endothelial Cells and Modulates Macrophages Function.

Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as , enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with on the antioxidant and immunomodulatory effects of Pushgay berries (, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.

Dementia and Related Comorbidity: Analysis of 2 Years of Admissions to Italian Hospitals.

Background: The aim of the present study was to examine the prevalence of dementia, related comorbidities, and mortality rates in hospitalized elderly patients in Italy.

Methods: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged 65 years or above admitted to acute Internal Medicine during 2 years (n=3,695,278 admissions). Discharge diagnoses were re-classified into 24 clusters, each including homogeneous diseases by the ICD-9-CM code classification.

Quantitative Trait Loci Mapping and Identification of Candidate Genes Linked to Fruit Acidity in Apricot ( L.).

Apricot breeding programs could be strongly improved by the availability of molecular markers linked to the main fruit quality traits. Fruit acidity is one of the key factors in consumer acceptance, but despite its importance, the molecular bases of this trait are still poorly understood. In order to increase the genetic knowledge on the fruit acidity, an F1 apricot population ('Lito' × 'BO81604311') has been phenotyped for titratable acidity and juice pH for the three following years.