A population based study to analyse amyotrophic lateral sclerosis as a multi-step process

Abstract Recent studies suggest that Amyotrophic Lateral Sclerosis (ALS) follows a multistep process. We evaluated this hypothesis in a well-defined ALS population in Palermo, Sicily, almost entirely followed by our ALS Clinical Center. Incident data from the ALS Center (2014–2023) were analyzed, in...

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Main Authors: Anna D’Amico, Roberta Cucunato, Giuseppe Salemi, Vincenzo La Bella, Paolo Aridon
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-89616-7
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author Anna D’Amico
Roberta Cucunato
Giuseppe Salemi
Vincenzo La Bella
Paolo Aridon
author_facet Anna D’Amico
Roberta Cucunato
Giuseppe Salemi
Vincenzo La Bella
Paolo Aridon
author_sort Anna D’Amico
collection DOAJ
description Abstract Recent studies suggest that Amyotrophic Lateral Sclerosis (ALS) follows a multistep process. We evaluated this hypothesis in a well-defined ALS population in Palermo, Sicily, almost entirely followed by our ALS Clinical Center. Incident data from the ALS Center (2014–2023) were analyzed, including both sporadic and familial ALS forms of the disease. To evaluate the multistep process, we regressed the natural log of age-specific incidence against the natural log of patient age We identified 216 ALS patients. We obtained a slope of 5 (r2 = 0.93); the 95% CI ranged from 2.51 to 7.60, remaining relatively wide due to the small sample size, with a p-value of 0.008. The slope estimate was consistent with a 6-step process. In the Palermo ALS population, the multistep analysis confirms a process consistent with a 6-step model. This data, obtained in a relatively homogeneous population, further highlights the probability of strict interaction between environmental and genetic variables in the disease. Our data offer insights into the complexity of the mechanisms involved in the pathogenesis of the disease, particularly during its asymptomatic phase. This study supports the hypothesis that a single therapeutic silver bullet would probably be insufficient to arrest or slow the disease’s progression.
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spelling doaj-art-d35df74643214b15bb1f427cefaa782a2025-08-20T01:56:01ZengNature PortfolioScientific Reports2045-23222025-04-011511810.1038/s41598-025-89616-7A population based study to analyse amyotrophic lateral sclerosis as a multi-step processAnna D’Amico0Roberta Cucunato1Giuseppe Salemi2Vincenzo La Bella3Paolo Aridon4Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of PalermoDepartment of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of PalermoDepartment of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of PalermoDepartment of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of PalermoDepartment of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of PalermoAbstract Recent studies suggest that Amyotrophic Lateral Sclerosis (ALS) follows a multistep process. We evaluated this hypothesis in a well-defined ALS population in Palermo, Sicily, almost entirely followed by our ALS Clinical Center. Incident data from the ALS Center (2014–2023) were analyzed, including both sporadic and familial ALS forms of the disease. To evaluate the multistep process, we regressed the natural log of age-specific incidence against the natural log of patient age We identified 216 ALS patients. We obtained a slope of 5 (r2 = 0.93); the 95% CI ranged from 2.51 to 7.60, remaining relatively wide due to the small sample size, with a p-value of 0.008. The slope estimate was consistent with a 6-step process. In the Palermo ALS population, the multistep analysis confirms a process consistent with a 6-step model. This data, obtained in a relatively homogeneous population, further highlights the probability of strict interaction between environmental and genetic variables in the disease. Our data offer insights into the complexity of the mechanisms involved in the pathogenesis of the disease, particularly during its asymptomatic phase. This study supports the hypothesis that a single therapeutic silver bullet would probably be insufficient to arrest or slow the disease’s progression.https://doi.org/10.1038/s41598-025-89616-7
spellingShingle Anna D’Amico
Roberta Cucunato
Giuseppe Salemi
Vincenzo La Bella
Paolo Aridon
A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
Scientific Reports
title A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
title_full A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
title_fullStr A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
title_full_unstemmed A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
title_short A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
title_sort population based study to analyse amyotrophic lateral sclerosis as a multi step process
url https://doi.org/10.1038/s41598-025-89616-7
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