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Accrued somatic mutations (nucleic acid changes) trigger ALS: 2005–2015 update
Author(s) -
Armon Carmel
Publication year - 2016
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25049
Subject(s) - amyotrophic lateral sclerosis , motor neuron , upper motor neuron , disease , somatic cell , age of onset , frontotemporal dementia , neuroscience , epidemiology , medicine , motor neurone disease , biology , pathology , genetics , gene , dementia
ABSTRACT Amyotrophic lateral sclerosis (ALS) is a multilevel disease of the motor neuron system. The mechanisms triggering disease onset should be considered separately from those facilitating its spread and motor neuron death. In 2005, I brought together clinical and epidemiological evidence to support the hypothesis that acquired nucleic acid changes may trigger sporadic ALS. Since 2005, the conceptual foundations for this hypothesis have been strengthened. The journal Amyotrophic Lateral Sclerosis was renamed Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration . The focal onset, with simultaneous initial maximal upper and lower motor neuron involvement in the region of onset, and patterns of spread, were characterized further. Clues from the epidemiology of sporadic ALS were affirmed by quantitative analysis, including the increase in disease incidence with age, suggesting accrual of time‐dependent changes, and the confirmation of smoking as an established risk factor. Additional observations support the conclusion that accrued somatic mutations trigger onset of ALS. Muscle Nerve 53 : 842–849, 2016