Molecular Pathology of ALS: What We Currently Know and What Important Information Is Still Missing
Open Access
- 29 July 2021
- journal article
- review article
- Published by MDPI AG in Diagnostics
- Vol. 11 (8), 1365
- https://doi.org/10.3390/diagnostics11081365
Abstract
Despite an early understanding of amyotrophic lateral sclerosis (ALS) as a disease affecting the motor system, including motoneurons in the motor cortex, brainstem, and spinal cord, today, many cases involving dementia and behavioral disorders are reported. Therefore, we currently divide ALS not only based on genetic predisposition into the most common sporadic variant (90% of cases) and the familial variant (10%), but also based on cognitive and/or behavioral symptoms, with five specific subgroups of clinical manifestation—ALS with cognitive impairment, ALS with behavioral impairment, ALS with combined cognitive and behavioral impairment, the fully developed behavioral variant of frontotemporal dementia in combination with ALS, and comorbid ALS and Alzheimer’s disease (AD). Generally, these cases are referred to as amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD). Clinical behaviors and the presence of the same pathognomonic deposits suggest that FTLD and ALS could be a continuum of one entity. This review was designed primarily to compare neuropathological findings in different types of ALS relative to their characteristic locations as well as the immunoreactivity of the inclusions, and thus, foster a better understanding of the immunoreactivity, distribution, and morphology of the pathological deposits in relation to genetic mutations, which can be useful in specifying the final diagnosis.Funding Information
- MH CZ – DRO: Conceptual Development of Research Organization, the General University Hospital, Prague (00064165, 00064190, NV19-04-00090, NV18-04-00179)
- Univerzita Karlova v Praze (GAUK 142120, Project Progress Q27/LF1)
This publication has 137 references indexed in Scilit:
- Protein aggregation in amyotrophic lateral sclerosisActa Neuropathologica, 2013
- Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosisNature, 2012
- TDP-43 functions and pathogenic mechanisms implicated in TDP-43 proteinopathiesTrends in Molecular Medicine, 2011
- Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALSNeuron, 2011
- A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTDNeuron, 2011
- Progranulin and TDP-43: Mechanistic Links and Future DirectionsJournal of Molecular Neuroscience, 2011
- Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementiaNature, 2011
- Differential Involvement of Optineurin in Amyotrophic Lateral Sclerosis With or Without SOD1 MutationsArchives of Neurology, 2011
- A harmonized classification system for FTLD-TDP pathologyActa Neuropathologica, 2011
- Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALSNature, 2010