Читать книгу Spectrums of Amyotrophic Lateral Sclerosis - Группа авторов - Страница 40

In comparison with the oligogenic model, a multistep model posits that ALS can be considered in terms of discrete etiological steps that each sequentially contributes to disease [8, 88]. Similar to cancer models, a single germline variant may be tolerated and not directly result in disease, but coupled with environmental exposure, additional variants, age‐related cellular damage, or yet unknown factors, ALS may rapidly occur once a step threshold has been reached [8, 88]. Because ALS has a strong association with increasing age [89], the multistep model is a logical framework to account for cell stress due to either long‐term environmental exposure or the ability of neurons to resist a variant's effect.