ALS: A bucket of genes, environment, metabolism and unknown ingredients.

Defining the genetic connection linking amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD)

1. Introduction: The autosomal dominant cerebellar ataxias (ADCA) are a clinically, pathologically and genetically heterogeneous group of neurodegenerative disorders caused by degeneration of cerebellum and its afferent and efferent connections. The degenerative process may additionally involves the ponto- medullar systems, pyramidal tracts, basal ganglia, cerebral cortex, peripheral nerves (ADCA I) and the retina (ADCA II), or can be limited to the cerebellum (ADCA III) (Harding et al., 1993). The most common of these dominantly inherited autosomal ataxias, ADCA I, includes many Spinocerebellar Ataxias (SCA) subtypes, some of which are caused by pathological CAG trinucleotide repeat expansion in the coding region on the mutated gene. Such is the case for SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA17 and Dentatorubral-pallidoluysian atrophy (DRPLA) (Matilla et al., 2006). Among the almost 30 SCAs, the variant SCA2 is the second most prevalent subtype worldwide, only surpassed by SCA3 (Schols et al., 2004; Matilla et al., 2006; Auburger, 2011)...

/pdf/spinocerebellar-ataxia-type-2-2zaphrslko.pdf

Spinocerebellar Ataxia Type 2

http://umu.diva-portal.org/smash/get/diva2:1095570/FULLTEXT01

ATXN2 trinucleotide repeat length correlates with risk of ALS

Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA–protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA–protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials. Magen et al. discovered new miRNA-based biomarkers in the blood of patients with ALS. miR-181 levels alone or in combination with an established protein biomarker predict ALS severity and prognosis and might enhance the power of clinical trials.

Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis.

Objective To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal and bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity. Methods In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months. Results Blood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity. Conclusions While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.

https://n.neurology.org/content/neurology/92/11/e1205.full.pdf

Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy

TDP-43 is the major disease protein in amyotrophic lateral sclerosis (ALS).1 Recently, ataxin-2, a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2 (SCA2),2 has been shown to interfere with TDP-43 toxicity in ALS animal models and to abnormally localize in ALS spinal cord neurons.3 An increased risk for ALS and an earlier age at disease onset were observed in patients with an intermediate-length CAG expansion (24–33) [(CAG)24–33] in ataxin-2 encoding gene ( ATXN2 ).

To test the hypothesis that ATXN2 (CAG)24–33 expansion is a clinical modifier in ALS, we determined the length of the polyQ expansion in 247 patients with ALS and correlated clinical phenotype in the (CAG)24–33 expansion patients with those with a CAG expansion below 24 repeats.

### Methods.

Considered in the present study were patients with ALS according to the El Escorial criteria4 evaluated at the ALS Clinic of Padova from January 2004 to August 2010. Patient data entered included sex, age and site of onset (bulbar or spinal), disease duration at ALS diagnosis, forced vital capacity (FVC, expressed as percentage of the expected value) at first assessment, survival defined as the time from onset to …

ALS risk but not phenotype is affected by ataxin-2 intermediate length polyglutamine expansion

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

G. Querin

Author Tools

Chat about Author

Papers

Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy

ALS risk but not phenotype is affected by ataxin-2 intermediate length polyglutamine expansion