Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Feb 5:14:42.
doi: 10.3389/fnins.2020.00042. eCollection 2020.

The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Yevgeniya A Abramzon  1   2 , Pietro Fratta  2 , Bryan J Traynor  1   3 , Ruth Chia  1
Affiliations
Review

The Overlapping Genetics of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Yevgeniya A Abramzon et al. Front Neurosci. .

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two diseases that form a broad neurodegenerative continuum. Considerable effort has been made to unravel the genetics of these disorders, and, based on this work, it is now clear that ALS and FTD have a significant genetic overlap. TARDBP, SQSTM1, VCP, FUS, TBK1, CHCHD10, and most importantly C9orf72, are the critical genetic players in these neurological disorders. Discoveries of these genes have implicated autophagy, RNA regulation, and vesicle and inclusion formation as the central pathways involved in neurodegeneration. Here we provide a summary of the significant genes identified in these two intrinsically linked neurodegenerative diseases and highlight the genetic and pathological overlaps.

Keywords: amyotrophic lateral sclerosis; frontotemporal dementia; neurodegeneration; neurological disorders; overlapping genetics.

PubMed Disclaimer

References

    1. Ajroud-Driss S., Fecto F., Ajroud K., Lalani I., Calvo S. E., Mootha V. K., et al. (2015). Mutation in the novel nuclear-encoded mitochondrial protein CHCHD10 in a family with autosomal dominant mitochondrial myopathy. Neurogenetics 16 1–9. 10.1007/s10048-014-0421-1 - DOI - PMC - PubMed
    1. Al-Obeidi E., Al-Tahan S., Surampalli A., Goyal N., Wang A. K., Hermann A., et al. (2018). Genotype-phenotype study in patients with valosin-containing protein mutations associated with multisystem proteinopathy. Clin. Genet. 93 119–125. 10.1111/cge.13095 - DOI - PMC - PubMed
    1. An H., Skelt L., Notaro A., Highley J. R., Fox A. H., La Bella V., et al. (2019). ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles. Acta Neuropathol. Commun. 7:7. 10.1186/s40478-019-0658-x - DOI - PMC - PubMed
    1. Anderson C. J., Bredvik K., Burstein S. R., Davis C., Meadows S. M., Dash J., et al. (2019). ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response. Acta Neuropathol. 138 103–121. 10.1007/s00401-019-01989-y - DOI - PMC - PubMed
    1. Arai T., Nonaka T., Hasegawa M., Akiyama H., Yoshida M., Hashizume Y., et al. (2003). Neuronal and glial inclusions in frontotemporal dementia with or without motor neuron disease are immunopositive for p62. Neurosci. Lett. 342 41–44. - PubMed