Comparison of family histories in FTLD subtypes and related tauopathies

Goldman, Jill; Farmer, Jennifer M.; Wood, Elisabeth McCarty; Johnson, Julene K.; Boxer, Adam L.; Neuhaus, John; Lomen‐Hoerth, Catherine; Wilhelmsen, Kirk C.; Lee, V. M.Y.; Grossman, Murray; Miller, Bruce L.

doi:10.1212/01.wnl.0000187068.92184.63

Cited by 319 publications

(220 citation statements)

References 10 publications

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“…As previously proposed by Goldman et al (2005), subjects were given a "Goldman score" ranging from 1 to 4, where 1 identifies an autosomal dominant family history of dementia, 2 identifies a familial aggregation of 3 or more family members with dementia, 3 identifies 1 other first degree relative with dementia, and 4 identifies no or unknown family history for dementia.…”

Section: Subjectsmentioning

confidence: 99%

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

Borroni

Alberici

Cercignani

et al. 2012

Neurobiology of Aging

103

112

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Granulin (GRN) mutations have been identified as a major cause of frontotemporal lobar degeneration (FTLD) by haploinsufficiency mechanism, although their effects on brain tissue dysfunction and damage still remain to be clarified. In this study, we investigated the pattern of neuroimaging abnormalities in FTLD patients, carriers and noncarriers of GRN Thr272fs mutation, and in presymptomatic carriers. We assessed regional gray matter (GM) atrophy, and resting (RS)-functional magnetic resonance imaging (fMRI). The functional connectivity maps of the salience (SN) and the default mode (DMN) networks were considered. Frontotemporal gray matter atrophy was found in all FTLD patients (more remarkably in those GRN Thr272fs carriers), but not in presymptomatic carriers. Functional connectivity within the SN was reduced in all FTLD patients (again more remarkably in those mutation carriers), while it was enhanced in the DMN. Conversely, presymptomatic carriers showed increased connectivity in the SN, with no changes in the DMN. Our findings suggest that compensatory mechanisms of brain plasticity are present in GRN-related FTLD, but with different patterns at a preclinical and symptomatic disease stage.

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Section: Subjectsmentioning

confidence: 99%

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

Borroni

Alberici

Cercignani

et al. 2012

Neurobiology of Aging

103

112

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show abstract

“…Thus, 223 probands with FTLD syndromes and 11 individuals with logopenic aphasia lacking a previously identified pathogenic mutation were included in the present screen for the C9ORF72 repeat expansion. Prior to screening, all cases within the cohort were assigned a modified Goldman score as a measure of the extent of family history of the disease (Goldman et al, 2005;Beck et al, 2008;Rohrer et al, 2009). A score of 1 represents an autosomal dominant family history of FTLD or MND; 2 is familial aggregation of three or more family members with dementia; 3 is one other first-degree relative with dementia of young onset (565 years); 3.5 is one other first-degree relative with dementia of onset 465 years of age; and 4 is no or unknown family history.…”

Section: Case Ascertainmentmentioning

confidence: 99%

O1‐05‐01: Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: Clinical, neuroanatomical and neuropathological features

Mahoney¹,

Beck²,

Rohrer

et al. 2012

Alzheimer's & Dementia

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An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43-68 years) and duration (1.7-22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration-TAR DNA-binding protein. These findings corroborate the clinical importance of the C9ORF72 mutation in frontotemporal lobar degeneration, delineate phenotypic and neuropathological features that could help to guide genetic testing, and suggest hypotheses for elucidating the neurobiology of a culprit subcortical network.

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“…1 The differential diagnosis for FTLD and AD has a potential impact for treatment and prognosis. [2][3][4] Currently available drugs such as the acetylcholinesterase (AchE) inhibitor for treating AD are often ineffective for the treatment of FTLD. 5 Furthermore, FTLD often shares clinical features with AD, whereas AD is often associated with FTLD clinical syndromes.…”

mentioning

confidence: 99%

Atrophy Measurement of the Anterior Commissure and Substantia Innominata with 3T High-Resolution MR Imaging: Does the Measurement Differ for Patients with Frontotemporal Lobar Degeneration and Alzheimer Disease and for Healthy Subjects?

Moon¹,

Kim²,

Ro³

et al. 2008

AJNR Am J Neuroradiol

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show abstract

Comparison of family histories in FTLD subtypes and related tauopathies

Cited by 319 publications

References 10 publications

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

Granulin mutation drives brain damage and reorganization from preclinical to symptomatic FTLD

O1‐05‐01: Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: Clinical, neuroanatomical and neuropathological features

Atrophy Measurement of the Anterior Commissure and Substantia Innominata with 3T High-Resolution MR Imaging: Does the Measurement Differ for Patients with Frontotemporal Lobar Degeneration and Alzheimer Disease and for Healthy Subjects?

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