Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study

Area of Science:

• Epidemiology
• Oncology
• Neurology

Background:

• Amyotrophic lateral sclerosis (ALS) shares epidemiological similarities with certain cancers, including later-life onset and rapid progression.
• The disease affects specific cell types and exhibits complex inheritance patterns.
• A cancer epidemiology model was adapted to explore ALS as a multistep process.

Purpose of the Study:

• To investigate the hypothesis that amyotrophic lateral sclerosis (ALS) develops through a multistep process.
• To apply a mathematical model, originally used for cancer research, to ALS incidence data.

Main Methods:

• Generated age and sex-specific incidence data for ALS from population registers in five European countries (Ireland, Netherlands, Italy, Scotland, England) between 1989 and 2012.
• Calculated age and sex-adjusted incidences for each register.
• Employed least squares regression to analyze the relationship between the logarithm of age-specific incidence and the logarithm of age.

Main Results:

• A total of 6274 ALS cases were identified across a population of approximately 34 million.
• A consistent linear relationship between log incidence and log age was observed across all five registers, with high R-squared values (0.95–0.99).
• The estimated slope of this relationship was approximately 4.8, suggesting a six-step process for ALS development, with similar estimates for men and women.

Conclusions:

• The linear relationship between log incidence and log age supports a multistage model for amyotrophic lateral sclerosis (ALS) pathogenesis.
• The findings suggest ALS is a six-step process, offering potential targets for future research.
• Identifying these discrete steps could pave the way for novel preventive strategies and therapeutic interventions for ALS.