Challenging the boundaries: c9orf72 mutation presenting as Alzheimer's disease.

C9orf72 hexanucleotide repeat expansion is a major cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), while its link with Alzheimer's disease (AD) is still unclear. We describe the case of a 53-year-old man with progressive memory and language deficits, mood disturbances, and a positive family history for ALS-FTD. Cerebrospinal fluid showed amyloid positivity, confirmed by amyloid-PET, with normal tau levels; [F]FDG-PET revealed an AD-like temporoparietal hypometabolism.

Exploring the phenotypic fingerprints of ANXA11 variants in ALS: a population-based study in an European cohort.

Background: Annexin A11 (ANXA11) has emerged as a significant gene associated with amyotrophic lateral sclerosis (ALS) and cognitive impairments. This study aimed to evaluate the prevalence and clinical and cognitive features of pathogenic variants in ANXA11 in an Italian ALS cohort.

Methods: Data were collected from the Piemonte and Valle d'Aosta Register for ALS between 2009 and 2020.

Identification of Transcriptomic Differences in Induced Pluripotent Stem Cells and Neural Progenitors from Amyotrophic Lateral Sclerosis Patients Carrying Different Mutations: A Pilot Study.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons with a phenotypic and genetic heterogeneity and elusive molecular mechanisms. With the present pilot study, we investigated different genetic mutations (, , and ) associated with ALS by generating induced pluripotent stem cells (iPSCs) from peripheral blood of ALS patients and healthy donors. iPSCs showed the typical morphology, expressed stem cell markers both at RNA (, , , and ) and protein (Oct4, Sox2, SSEA3, and Tra1-60) levels.

Cortical Excitability as a Prognostic and Phenotypic Stratification Biomarker in Amyotrophic Lateral Sclerosis.

Objective: Despite its clinical heterogeneity, amyotrophic lateral sclerosis is unified by early and prominent alterations in cortical excitability, increasingly recognized as contributors to disease progression. This study assessed whether the ratio between motor evoked potential (MEP) amplitude, reflecting upper motor neuron integrity, and compound muscle action potential (CMAP) amplitude, indexing lower motor neuron function, could provide an accessible marker of corticospinal excitability to stratify patients by phenotype, stage, and survival.

Methods: In this multicenter retrospective study, 743 amyotrophic lateral sclerosis patients from 16 tertiary centers in Italy were analyzed.

Neutrophil-to-Lymphocyte Ratio in the Alzheimer's Disease Continuum.

Alzheimer's disease (AD) is a neurodegenerative disorder defined clinically by progressive cognitive decline and memory impairment and pathologically by the accumulation of amyloid-beta plaques, tau neurofibrillary tangles, neuroinflammation, and immune system dysregulation. Peripheral biomarkers are gaining attention as valuable tools for elucidating neuroinflammatory mechanisms in the AD continuum, with potential implications for diagnosis and prognosis. Among these, the neutrophil-to-lymphocyte ratio (NLR) has emerged as a promising systemic inflammatory marker.

Recent therapeutic advances in the treatment and management of amyotrophic lateral sclerosis: the era of regenerative medicine.

Introduction: Despite decades of research, effective disease-modifying treatments for Amyotrophic Lateral Sclerosis (ALS) remain scarce. The emergence of regenerative medicine presents a new frontier for ALS treatment.

Areas Covered: This review is based on a comprehensive literature search using PubMed, Scopus and clinical trials databases on the recent therapeutic advancements in ALS, giving focus to regenerative medicine.

Phosphatemia is an Independent Prognostic Factor in Amyotrophic Lateral Sclerosis.

Objective: The objective of this study was to evaluate the prognostic value of several muscle damage biomarkers.

Methods: Data from Piemonte and Valle d'Aosta Amyotrophic Lateral Sclerosis (PARALS) were considered for this study. Survival was defined as the time from diagnosis to death, tracheostomy, or the censoring date.

Neuroglia in neurodegeneration: Amyotrophic lateral sclerosis and frontotemporal dementia.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurodegenerative diseases sharing significant pathologic and genetic overlap, leading to consider these diseases as a continuum in the spectrum of their pathologic features. Although FTD compromises only specific brain districts, while ALS involves both the nervous system and the skeletal muscles, several neurocentric mechanisms are in common between ALS and FTD. Also, recent research has revealed the significant involvement of nonneuronal cells, particularly glial cells such as astrocytes, oligodendrocytes, microglia, and peripheral immune cells, in disease pathology.

Changes to Average Survival of Patients With Amyotrophic Lateral Sclerosis (1995-2018): Results From the Piemonte and Valle d'Aosta Registry.

Background And Objectives: The average survival of patients with amyotrophic lateral sclerosis (ALS) ranges from 2 to 5 years from symptom onset. However, it remains unclear whether this estimate has improved over time. The objective of this study was to analyze the survival trend of a large population-based cohort of patients with ALS over a 24-year period.

Lower Circulating Gas6 Levels Are Associated with Bulbar Phenotype and Faster Disease Progression in Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects the motor neurons in the brain and spinal cord. While the exact cause of ALS is not fully understood, a combination of genetic and environmental factors is believed to contribute to its development. Growth arrest-specific 6 (Gas6), a vitamin K-dependent protein, has been recognized to enhance oligodendrocytes and neurons' survival and is associated with different kinds of (neuro)inflammatory conditions.

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.