Frontotemporal dementia: a bridge between dementia and neuromuscular disease

Ng, Adeline Su Lyn; Rademakers, Rosa; Miller, Bruce L.

doi:10.1111/nyas.12638

Cited by 101 publications

(93 citation statements)

References 219 publications

(280 reference statements)

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“…Both familial ALS (fALS) and sporadic ALS (sALS) can develop concurrently with frontotemporal lobar dementia (FTLD). By contrast with the dementia of Alzheimer disease (AD), in which the cardinal finding is memory loss, FTLD is characterized by behavioral changes and progressive aphasia, sometimes accompanied by movement disorders (7,8). While AD involves prominent pathology in the hippocampus, the essential finding in FTLD is, as the name suggests, early atrophy of the frontal and temporal lobes.…”

Section: Introductionmentioning

confidence: 99%

Emerging mechanisms of molecular pathology in ALS

Peters¹,

Ghasemi²,

Brown³

2015

J. Clin. Invest.

238

142

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Section: Introductionmentioning

confidence: 99%

Emerging mechanisms of molecular pathology in ALS

Peters¹,

Ghasemi²,

Brown³

2015

J. Clin. Invest.

238

142

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“…3 Most healthy individuals carry up to 25 repeats, with more than half carrying only two repeats, while pathogenic expansions of hundreds 2 to several thousands have been reported in FTD and ALS. 1 6 In C9orf72-related disease, a repeat length of >30 has typically been defined as pathogenic, 2 mainly due to technical limitations of the repeat-primed PCR (rp-PCR) technique.…”

Section: Introductionmentioning

confidence: 99%

Intermediate C9orf72 alleles in neurological disorders: does size really matter?

Tan

2017

J Med Genet

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C9orf72 repeat expansions is a major cause of familial frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) worldwide. Sizes of <20 hexanucleotide repeats are observed in controls, while up to thousands associate with disease. Intermediate C9orf72 repeat lengths, however, remain uncertain. We systematically reviewed the role of intermediate C9orf72 alleles in C9orf72-related neurological disorders. We identified 49 studies with adequate available data on normal or intermediate C9orf72 repeat length, involving subjects with FTD, ALS, Parkinson’s disease (PD), atypical parkinsonism, Alzheimer’s disease (AD) and other aetiologies. We found that, overall, normal or intermediate C9orf72 repeat lengths are not associated with higher disease risk across these disorders, but intermediate allele sizes appear to associate more frequently with neuropsychiatric phenotypes. Intermediate sizes were detected in subjects with personal or family history of FTD and/or psychiatric illness, parkinsonism complicated by psychosis and rarely in psychiatric cohorts. Length of the hexanucleotide repeat may be influenced by ethnicity (with Asian controls displaying shorter normal repeat lengths compared with Caucasians) and underlying haplotype, with more patients and controls carrying the ‘risk’ haplotype rs3849942 displaying intermediate alleles. There is some evidence that intermediate alleles display increased methylation levels and affect normal transcriptional activity of the C9orf72 promoter, but the ‘critical’ repeat size required for initiation of neurodegeneration remains unknown and requires further study. In common neurological diseases, intermediate C9orf72 repeats do not influence disease risk but may associate with higher frequency of neuropsychiatric symptoms. This has important clinical relevance as intermediate carriers pose a challenge for genetic counselling.

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“…19 21 The majority of FTD syndromes, including bvFTD, show pathological substrates involving either TDP-43 (50%) or τ (40%). 22 Although a direct mechanistic link between TBI and these pathological processes is lacking, some evidence suggests that these may be related. In nearly all severities of acute TBI, axonal tracts stretch, shear and compress, often resulting in diffuse axonal injury.…”

Section: Introductionmentioning

confidence: 99%

Traumatic brain injury history is associated with earlier age of onset of frontotemporal dementia: Table 1

LoBue

Wilmoth

Cullum

et al. 2015

J Neurol Neurosurg Psychiatry

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Objective We retrospectively examined whether a history of traumatic brain injury (TBI) is associated with an earlier age of symptom onset and diagnosis in a large sample of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Subjects with bvFTD (n=678) were obtained from the National Alzheimer's Coordinating Center Uniform Data Set. TBI was categorized based on reported lifetime history of TBI with loss of consciousness (LOC) but no chronic deficits occurring more than one year prior to diagnosis of bvFTD. ANCOVA was used to determine if clinician-estimated age of symptom onset and age at diagnosis of bvFTD differed between those who reported a history of TBI with LOC (TBI+) and those who did not (TBI-). Results Controlling for sex, the TBI+ bvFTD group had an earlier age of symptom onset and age of diagnosis that was on average 2.8 and 3.2 years earlier (p's<.01) than the TBI- bvFTD group. Conclusion TBI history with LOC occurring more than one year prior to diagnosis is associated with an earlier age of symptom onset and diagnosis in patients with bvFTD. TBI may be related to the underlying neurodegenerative processes in bvFTD, but the implications of age at time of injury, severity, and repetitive injuries remain unclear.

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Frontotemporal dementia: a bridge between dementia and neuromuscular disease

Cited by 101 publications

References 219 publications

Emerging mechanisms of molecular pathology in ALS

Emerging mechanisms of molecular pathology in ALS

Intermediate C9orf72 alleles in neurological disorders: does size really matter?

Traumatic brain injury history is associated with earlier age of onset of frontotemporal dementia: Table 1

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