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Focus on the heterogeneity of amyotrophic lateral sclerosis

The clinical manifestations of amyotrophic lateral sclerosis (ALS) are variable in terms of age at disease onset, site of onset, progression of symptoms, motor neuron involvement, and the occurrence of cognitive and behavioral changes. Genetic background is a key determinant of the ALS phenotype. Th...

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Main Authors: Bendotti, Caterina (Author) , Bonetto, Valentina (Author) , Pupillo, Elisabetta (Author) , Logroscino, Giancarlo (Author) , Al-Chalabi, Ammar (Author) , Lunetta, Christian (Author) , Riva, Nilo (Author) , Mora, Gabriela (Author) , Lauria, Giuseppe (Author) , Weishaupt, Jochen H. (Author) , Agosta, Federica (Author) , Malaspina, Andrea (Author) , Basso, Manuela (Author) , Greensmith, Linda (Author) , Bosch, Ludo Van Den (Author) , Ratti, Antonia (Author) , Corbo, Massimo (Author) , Hardiman, Orla (Author) , Chiò, Adriano (Author) , Silani, Vincenzo (Author) , Beghi, Ettore (Author)
Format: Article (Journal)
Language:English
Published: 25 Jun 2020
In: Amyotrophic lateral sclerosis & frontotemporal degeneration
Year: 2020, Volume: 21, Issue: 7/8, Pages: 485-495
ISSN:2167-9223
DOI:10.1080/21678421.2020.1779298
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/21678421.2020.1779298
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Author Notes:Caterina Bendotti, Valentina Bonetto, Elisabetta Pupillo, Giancarlo Logroscino, Ammar Al-Chalabi, Christian Lunetta, Nilo Riva, Gabriela Mora, Giuseppe Lauria, Jochen H. Weishaupt, Federica Agosta, Andrea Malaspina, Manuela Basso, Linda Greensmith, Ludo Van Den Bosch, Antonia Ratti, Massimo Corbo, Orla Hardiman, Adriano Chiò, Vincenzo Silani, Ettore Beghi
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Summary:The clinical manifestations of amyotrophic lateral sclerosis (ALS) are variable in terms of age at disease onset, site of onset, progression of symptoms, motor neuron involvement, and the occurrence of cognitive and behavioral changes. Genetic background is a key determinant of the ALS phenotype. The mortality of the disease also varies with the ancestral origin of the affected population and environmental factors are likely to be associated with ALS at least within some cohorts. Disease heterogeneity is likely underpinned by the presence of different pathogenic mechanisms. A variety of ALS animal models can be informative about the heterogeneity of the neuropathological or genetic aspects of the disease and can support the development of new therapeutic intervention. Evolving biomarkers can contribute to the identification of differing genotypes and phenotypes, and can be used to explore whether genotypic and phenotypic differences in animal models might help to provide a better definition of the heterogeneity of ALS in humans. These include neurofilaments, peripheral blood mononuclear cells, extracellular vesicles, microRNA and imaging findings. These biomarkers might predict not only the development of the disease, but also the variability in progression, although robust validation is required. A promising area of progress in modeling the heterogeneity of human ALS is represented by the use of human induced pluripotent stem cell (iPSCs)-derived motor neurons. Although the translational value of iPSCs remains unclear, this model is attractive in the perspective of replicating the heterogeneity of sporadic ALS as a first step toward a personalized medicine strategy.
Item Description:Gesehen am 07.04.2021
Physical Description:Online Resource
ISSN:2167-9223
DOI:10.1080/21678421.2020.1779298

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