The C9orf72 hexanucleotide repeat expansion in FTD and ALS

Department of Pathology and Northwestern University Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, 710 North Fairbanks Court, Olson 2-458, Chicago, IL 60611, USA. .
Nature Reviews Neurology (Impact Factor: 14.1). 04/2012; 8(5):249-50. DOI: 10.1038/nrneurol.2012.58
Source: PubMed
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Frontotemporal dementias are neurodegenerative diseases in which symptoms of frontal and/or temporal lobe disease are the first signs of the illness, and as the diseases progress, they resemble a focal left hemisphere process such as stroke or traumatic brain injury, even more than a neurodegenerative disease. Over time, some patients develop a more generalized dementia. Four clinical subtypes characterize the predominant presentations of this illness: behavioral or frontal variant FTD, progressive nonfluent aphasia, semantic dementia, and logopenic primary progressive aphasia. These clinical variants correlate with regional patterns of atrophy on brain imaging studies such as MRI and PET scanning, as well as with biochemical and molecular genetic variants of the disorder. The treatment is as yet only symptomatic, but advances in molecular genetics promise new therapies.
    Neuropsychiatric Disease and Treatment 06/2014; 10:1045-55. DOI:10.2147/NDT.S38821 · 2.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A growing body of evidence indicates that neurodegenerative motor disorders involved high-order cognitive dysfunctions. Crucially, evidence obtained in multiple behavioral, neuroimaging, and electrophysiological studies points to selective impairments of action language -that is, processing of linguistic stimuli denoting motor actions, including idioms (e.g., cut a rug) and action verbs (e.g., clap). Action-verb deficits (with relative preservation of noun processing) have been repeatedly documented in Parkinson’s disease (PD). However, research on relevant biomarkers is still scant, and clinical implications of these findings have not yet been formally discussed. Relevant insights may be obtained through the assessment of motor-language coupling (i.e., the behavioral and neural integration of action-verb processing and ongoing motor actions). We propose that motorlanguage coupling deficits, as indexed by a cortical-subcortical network, may constitute an early neurocognitive marker of PD. Specifically, deficits in this domain at the prodromal stage may be detected through the actionsentence compatibility (ACE) paradigm, which induces a contextual coupling of ongoing motor actions and action-verb processing. Our translational proposal is supported and illustrated by recent studies demonstrating the sensitivity of the ACE technique as well as its potential to assist in differential diagnosis and interventionprogram design.
    06/2014; 5(2):152-159. DOI:10.2478/s13380-014-0218-6
  • [Show abstract] [Hide abstract]
    ABSTRACT: Within the last decade, the neurobiology of action processing has moved from an obscure topic of specialist interest to one of the most popular themes in modern neuroscience. However, the wealth of literature and the diversity of approaches and theoretical models can make the field complex and, at times, bewildering. This review presents the main currents of research, examining their theoretical underpinnings in an interdisciplinary context. The presence of specific deficits in verb and action processing has been documented in a wide range of neurodegenerative diseases, including parkinsonian syndromes and motor neuron disease. Interestingly, most of these disorders affect the motor system, suggesting a systematic relationship between motor functions and their cognitive and linguistic representations. Action processing has been explored with a whole spectrum of methodologies, from neuroimaging to transcranial and intracranial stimulation. The findings have been integrated with other influential concepts and theories, including mirror neurons and embodied cognition. Converging evidence from patient and imaging studies links the concepts of actions and their processing with the execution of actions through the motor system. The theory of embodied cognition remains influential as well as controversial. However, the points of criticism have changed, reflecting recent paradigm shifts.
    Current opinion in neurology 10/2013; DOI:10.1097/WCO.0000000000000039 · 5.73 Impact Factor