Croplands proximity is associated with amyotrophic lateral sclerosis incidence and age at onset.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from an intricate interplay between genetics and environmental factors. Many studies have explored living in rural areas as a possible risk factor for ALS, without focusing simultaneously on incidence, age at onset and phenotypic features.

Objective: To evaluate the effect of croplands residential proximity on ALS incidence and phenotype, focusing on age of onset, site of onset and progression rate.

Circulating GLAST EVs are increased in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, hallmarked by the gradual deterioration of motor neurons, culminating in muscle weakness and fatal paralysis. The exact etiology of ALS remains elusive, and there is a critical need for reliable biomarkers to aid in diagnosis and monitoring of disease progression. Extracellular vesicles (EVs) have emerged as promising candidates for biomarker discovery in neurodegenerative diseases such as ALS, giving access to pathologically relevant tissues otherwise typically challenging or invasive to sample.

From Mild Cognitive Impairment to Dementia: The Impact of Comorbid Conditions on Disease Conversion.

The conversion from mild cognitive impairment (MCI) to dementia is influenced by several factors, including comorbid conditions such as metabolic and vascular diseases. Understanding the impact of these comorbidities can help in the disease management of patients with a higher risk of progressing to dementia, improving outcomes. In the current study, we aimed to analyze data from a large cohort of MCI (n = 188) by principal component analysis (PCA) and cluster analysis (CA) to classify patients into distinct groups based on their comorbidity profile and to predict the risk of conversion to dementia.

Current status and new avenues of stem cell-based preclinical and therapeutic approaches in amyotrophic lateral sclerosis.

Introduction: Cell therapy development represents a critical challenge in amyotrophic lateral sclerosis (ALS) research. Despite more than 20 years of basic and clinical research, no definitive safety and efficacy results of cell-based therapies for ALS have been published.

Areas Covered: This review summarizes advances using stem cells (SCs) in pre-clinical studies to promote clinical translation and in clinical trials to treat ALS.

Coupling motor evoked potentials and brain [F]FDG-PET in Amyotrophic Lateral Sclerosis: preliminary findings on disease severity.

Background: The diagnosis of amyotrophic lateral sclerosis (ALS) is primarily clinical, supported by the electromyographic examination to reveal signs of lower motor neuron damage. Identifying reliable markers of upper motor neuron (UMN) involvement is challenging. On this regard, the role of transcranial magnetic stimulation-induced motor-evoked potentials (TMS-MEPs), and its relationship with UMN burden, is still under investigation.

Shotgun Proteomics Links Proteoglycan-4 Extracellular Vesicles to Cognitive Protection in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder lacking reliable biomarkers for early diagnosis and disease progression monitoring. This study aimed to identify the novel biomarkers in plasmatic extracellular vesicles (EVs) isolated from ALS patients and healthy controls (HCs). A total of 61 ALS patients and 30 age-matched HCs were enrolled in the study and the protein content of circulating EVs was analyzed by shotgun proteomics.

Novel Therapeutic Strategies in Alzheimer's Disease: Pitfalls and Challenges of Anti-Amyloid Therapies and Beyond.

Alzheimer's disease (AD) causes a significant challenge to global healthcare systems, with limited effective treatments available. This review examines the landscape of novel therapeutic strategies for AD, focusing on the shortcomings of traditional therapies against amyloid-beta (Aβ) and exploring emerging alternatives. Despite decades of research emphasizing the role of Aβ accumulation in AD pathogenesis, clinical trials targeting Aβ have obtained disappointing results, highlighting the complexity of AD pathophysiology and the need for investigating other therapeutic approaches.

Sex Differences in Amyotrophic Lateral Sclerosis Survival and Progression: A Multidimensional Analysis.

Objective: To investigate sex-related differences in amyotrophic lateral sclerosis (ALS) prognosis and their contributing factors.

Methods: Our primary cohort was the Piemonte and Aosta Register for ALS (PARALS); the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) and the Answer ALS databases were used for validation. Survival analyses were conducted accounting for age and onset site.

Variability in Clinical Phenotype in TARDBP Mutations: Amyotrophic Lateral Sclerosis Case Description and Literature Review.

Mutations in the 43 kDa transactive-response (TAR)-DNA-binding protein () are associated with 2-5% of familial Amyotrophic Lateral Sclerosis (ALS) cases. TAR DNA-Binding Protein 43 (TDP-43) is an RNA/DNA-binding protein involved in several cellular mechanisms (e.g.

Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.

Many potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases, such as Alzheimer's (AD) disease, Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), as well as in a seemingly distinct Niemann-Pick type C disease with primarily juvenile onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets, such as microglia, peripheral macrophages, and regulatory T cells (Tregs); the complement system; and other soluble factors.

Effects of Acetyl-L-Carnitine on Oxidative Stress in Amyotrophic Lateral Sclerosis Patients: Evaluation on Plasma Markers and Members of the Neurovascular Unit.

Oxidative stress, the alteration of mitochondrial function, and the neurovascular unit (NVU), play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. We aimed to demonstrate the changes in the plasma redox system and nitric oxide (NO) in 32 new ALS-diagnosed patients in treatment with Acetyl-L-Carnitine (ALCAR) compared to healthy controls. We also evaluated the effects of plasma on human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes.

Predictors for progression in amyotrophic lateral sclerosis associated to SOD1 mutation: insight from two population-based registries.

Background: Uncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient' counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype-phenotype correlations and factors that potentially impact disease progression.

Methods: This is a retrospective observational study of a SOD1-ALS cohort from two Italian registers situated in the regions of Emilia-Romagna, Piedmont and Valle d'Aosta.

Neuroinflammatory Pathways in the ALS-FTD Continuum: A Focus on Genetic Variants.

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal dementia (FDT) are progressive neurodegenerative disorders that, in several cases, overlap in clinical presentation, and genetic and pathological disease mechanisms. About 10-15% of ALS cases and up to 40% of FTD are familial, usually with dominant traits. ALS and FTD, in several cases, share common gene mutations, such as in , , , , , , and .

Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis.

In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m/day,1 mg/m/day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained.

The role of peripheral immunity in ALS: a population-based study.

Background: Systemic inflammation has been proposed as a relevant mechanism in amyotrophic lateral sclerosis (ALS). Still, comprehensive data on ALS patients' innate and adaptive immune responses and their effect on the clinical phenotype are lacking. Here, we investigate systemic immunity in a population-based ALS cohort using readily available hematological indexes.

The pivotal role of high-resolution mass spectrometry in the study of grape glycosidic volatile precursors for the selection of grapevines resistant to mildews.

A breeding program to produce new grape varieties tolerant to main vine fungal pathogens (Plasmopara viticola and Erysiphe necator) is carrying out by crossing Vitis vinifera cv. "Glera" with resistant genotypes such as "Solaris," "Bronner," and "Kunleany." Firstly, resistance gene-based markers analyses allowed the identification of five genotypes, which have inherited the resistance loci against mildews.

Investigating the Prognostic Role of Peripheral Inflammatory Markers in Mild Cognitive Impairment.

Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases. Peripheral markers of inflammation, including blood cell counts and their ratios, such as the neutrophil-to-lymphocyte ratio (NLR), have been reported as an easily accessible and reliable proxy of central nervous system inflammation. However, the role of peripheral inflammation in dementia and Mild Cognitive Impairment (MCI) still needs to be clarified.

Retrospective observational study on the use of acetyl-L-carnitine in ALS.

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC.

Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder.

Proteinopathy and neuroinflammation are two main hallmarks of neurodegenerative diseases. They also represent rare common events in an exceptionally broad landscape of genetic, environmental, neuropathologic, and clinical heterogeneity present in patients. Here, we aim to recount the emerging trends in amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) spectrum disorder.

New Insights into the Relationship between Nutrition and Neuroinflammation in Alzheimer's Disease: Preventive and Therapeutic Perspectives.

Neurodegenerative diseases are progressive brain disorders characterized by inexorable synaptic dysfunction and neuronal loss. Since the most consistent risk factor for developing neurodegenerative diseases is aging, the prevalence of these disorders is intended to increase with increasing life expectancy. Alzheimer's disease is the most common cause of neurodegenerative dementia, representing a significant medical, social, and economic burden worldwide.

iPSC-based research in ALS precision medicine.

Clinical trials in amyotrophic lateral sclerosis (ALS) are challenged by the lack of pre-clinical models and biomarkers of disease onset and progression. In this issue, Morimoto et al. use induced pluripotent stem cell (iPSC)-derived motor neurons from patients with ALS to study therapeutic mechanisms of ropinirole in a clinical trial and identify treatment responders.