Distinct clinical and pathological phenotypes in frontotemporal dementia associated with MAPT, PGRN and C9orf72 mutations

Snowden, Julie S.; Adams, J. E.; Harris, Jennifer; Thompson, James C.; Rollinson, Sara; Richardson, Anna; Jones, Matthew; Neary, David; Mann, David; Pickering‐Brown, Stuart

doi:10.3109/21678421.2015.1074700

Cited by 88 publications

(108 citation statements)

References 40 publications

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“…MAPT mutations have been associated with pure FTD [16] and with FTD with parkinsonism and/or MND [7, 9, 11, 17], but also with progressive sopranuclear paralysis and Alzheimer disease [18, 19]. …”

Section: Discussionmentioning

confidence: 99%

Role of MAPT in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients

et al. 2018

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The aim of our study was to evaluate the role of mutations in the MAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, including MAPT, known to be associated with ALS and frontotemporal dementia. The presence of the C9orf72 expansion was also investigated. Twelve patients had mutations in the SOD1, TARDBP, MATR3, and FUS genes, while 10 patients carried the C9orf72 expansion. One female patient was found to carry the D348G mutation in MAPT, previously reported in an Italian family with lower motor neuron disease. Our patient presented both upper and lower motor neuron signs, early development of dyspnea, resting and kinetic tremor, and a slow disease course (> 11 years). The present case further broadens the clinical phenotype associated with MAPT mutations and suggests that, although rarely, MAPT mutations can cause ALS and, therefore, should be analyzed in ALS patients, especially in those with early breathing difficulties and long-lasting disease.

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Section: Discussionmentioning

confidence: 99%

Role of MAPT in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients

et al. 2018

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“…TANK-binding kinase 1 ( TBK1 ) mutations have also been reported to cause FTD–MND spectrum disorders 128 . GRN mutations cause about 25% of familial cases of FTLD-TDP 129 , and typically give rise to a bvFTD syndrome or, less commonly, CBS, language or mixed behavioural–language FTD 130,131 . TARDBP mutations are responsible for 4% of familial ALS cases reported, and only rarely cause FTD.…”

Section: Frontotemporal Dementiamentioning

confidence: 99%

A clinicopathological approach to the diagnosis of dementia

2017

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The most definitive classification systems for dementia are based on the underlying pathology which, in turn, is categorized largely according to the observed accumulation of abnormal protein aggregates in neurons and glia. These aggregates perturb molecular processes, cellular functions and, ultimately, cell survival, with ensuing disruption of large-scale neural networks subserving cognitive, behavioural and sensorimotor functions. The functional domains affected and the evolution of deficits in these domains over time serve as footprints that the clinician can trace back with various levels of certainty to the underlying neuropathology. The process of phenotyping and syndromic classification has substantially improved over decades of careful clinicopathological correlation, and through the discovery of in vivo biomarkers of disease. Here, we present an overview of the salient features of the most common dementia subtypes — Alzheimer disease, vascular dementia, frontotemporal dementia and related syndromes, Lewy body dementias, and prion diseases — with an emphasis on neuropathology, relevant epidemiology, risk factors, and signature signs and symptoms.

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“…Mean disease duration is 8 years (Snowden et al . ), but with a wide range of 5–30 years (Seelaar et al . ).…”

Section: Clinical Syndromes Of Familial Ftdmentioning

confidence: 99%

The clinical spectrum of sporadic and familial forms of frontotemporal dementia

Woollacott

Rohrer

2016

Journal of Neurochemistry

122

115

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The term frontotemporal dementia (FTD) describes a clinically, genetically and pathologically diverse group of neurodegenerative disorders. Symptoms of FTD can present in individuals in their 20s through to their 90s, but the mean age at onset is in the sixth decade. The most common presentation is with a change in personality and impaired social conduct (behavioural variant FTD). Less frequently patients present with language problems (primary progressive aphasia). Both of these groups of patients can develop motor features consistent with either motor neuron disease (usually the amyotrophic lateral sclerosis variant) or parkinsonism (most commonly a progressive supranuclear palsy or corticobasal syndrome). In about a third of cases FTD is familial, with mutations in the progranulin, microtubule-associated protein tau and chromosome 9 open reading frame 72 genes being the major causes. Mutations in a number of other genes including TANK-binding kinase 1 are rare causes of familial FTD. This review aims to clarify the often confusing terminology of FTD, and outline the various clinical features and diagnostic criteria of sporadic and familial FTD syndromes. It will also discuss the current major challenges in FTD research and clinical practice, and potential areas for future research.

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Distinct clinical and pathological phenotypes in frontotemporal dementia associated with MAPT, PGRN and C9orf72 mutations

Cited by 88 publications

References 40 publications

Role of <b><i>MAPT</i></b> in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients

Role of <b><i>MAPT</i></b> in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients

A clinicopathological approach to the diagnosis of dementia

The clinical spectrum of sporadic and familial forms of frontotemporal dementia

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