Frontotemporal dementia: A bridge between dementia and neuromuscular disease

Adeline S L Ng, Rosa V Rademakers, Bruce L. Miller

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The concept that frontotemporal dementia (FTD) is a purely cortical dementia has largely been refuted by the recognition of its close association with motor neuron disease, and the identification of transactive response DNA-binding protein 43 (TDP-43) as a major pathological substrate underlying both diseases. Genetic findings have transformed this field and revealed connections between disorders that were previous thought clinically unrelated. The discovery that the C9ORF72 locus is responsible for the majority of hereditary FTD, amyotrophic lateral sclerosis (ALS), and FTD-ALS cases and the understanding that repeat-containing RNA plays a crucial role in pathogenesis of both disorders has paved the way for the development of potential biomarkers and therapeutic targets for these devastating diseases. In this review, we summarize the historical aspects leading up to our current understanding of the genetic, clinical, and neuropathological overlap between FTD and ALS, and include brief discussions on chronic traumatic encephalopathy (CTE), given its association with TDP-43 pathology, its associated increased dementia risk, and reports of ALS in CTE patients. In addition, we describe other genetic associations between dementia and neuromuscular disease, such as inclusion body myositis with Paget's disease and FTD.

Original languageEnglish (US)
Pages (from-to)71-93
Number of pages23
JournalAnnals of the New York Academy of Sciences
Volume1338
Issue number1
DOIs
StatePublished - Mar 1 2015

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Frontotemporal Dementia
Neuromuscular Diseases
Dementia
DNA-Binding Proteins
Inclusion Body Myositis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Association reactions
Biomarkers
History
RNA
Pathology
Neurons
Frontotemporal Dementia With Motor Neuron Disease
Neuromuscular Disease
Substrates
Chronic Traumatic Encephalopathy
Therapeutics

Keywords

  • Amyotrophic lateral sclerosis
  • C9ORF72
  • Frontotemporal dementia
  • Motor neuron disease
  • Neuromuscular disease

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Cite this

Frontotemporal dementia : A bridge between dementia and neuromuscular disease. / Ng, Adeline S L; Rademakers, Rosa V; Miller, Bruce L.

In: Annals of the New York Academy of Sciences, Vol. 1338, No. 1, 01.03.2015, p. 71-93.

Research output: Contribution to journalArticle

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