Temporal Variant Frontotemporal Dementia Is Associated with Globular Glial Tauopathy

Clark, Camilla N.; Lashley, Tammaryn; Mahoney, Colin; Warren, Jason D.; Révész, Tamás; Rohrer, Jonathan D.

doi:10.1097/wnn.0000000000000060

Cited by 20 publications

(37 citation statements)

References 15 publications

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“…There were no significant differences between Patient 1 with p.P301L from this study and previously published sporadic patients with GGT, including five patients from the Mayo Clinic brain bank []. All sporadic patients with GGT had frontotemporal lobar atrophy with brain weights ranging from 960 to 1300 g [].…”

Section: Discussionmentioning

confidence: 69%

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) due to microtubule‐associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy

Tacik

Sanchez‐Contreras

DeTure

et al. 2017

Neuropathology Appl Neurobio

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Aim The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. Methods Genealogical, clinical, neuropathologic, and genetic data were reviewed from eight individuals. Results The series consisted of five men and three women with an average age of death of 58 years (52–65 years) and average disease duration of 9 years (3–14 years). The first symptoms were those of behavioral variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ε3/ε3 in seven and ε3/ε4 in one. The average brain weight was 1015 grams (876 – 1188 grams). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, while there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). Conclusions This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

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Section: Discussionmentioning

confidence: 69%

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) due to microtubule‐associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy

Tacik

Sanchez‐Contreras

DeTure

et al. 2017

Neuropathology Appl Neurobio

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“…The “atypical” svPPA-tau cases showed greater executive and motor involvement and a trend toward more severe behavioral symptoms (apathy and/or disinhibition), likely in relation to greater atrophy of frontotemporal cortex (i.e., medial ATL, OFC, ACC), basal ganglia, and connecting WM structures 15,42 . Although disease duration might be a factor in determining these differences, atypical symptoms were also present in svPPA-tau cases with comparable age and disease duration relative to svPPA-TDP.…”

Section: Discussionmentioning

confidence: 99%

Typical and atypical pathology in primary progressive aphasia variants

Spinelli

Mandelli

Miller

et al. 2017

Annals of Neurology

323

340

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Objective To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. Methods Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 non-fluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of grey matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms. Results A clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with TDP inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer’s disease (AD) pathology in 19% of cases. Each variant was associated with one typical pathology: 24/29 (83%) svPPA showed FTLD-TDP type C, 22/25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick’s disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants. Interpretation Each PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo.

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“…[13][14][15][16][17][18][19][20][21][22][23][24] In cases with detailed descriptions, the clinical diagnoses were FTLD in 14 cases, progressive non-fluent aphasia in three cases, semantic dementia in one case, MND in five cases, PLS in three cases, Alzheimer's disease in four cases, PSP in six cases, multiple system atrophy one case, corticobasal syndrome (CBS) in two cases, and one case of Creutzfeldt-Jakob disease. [13][14][15][16][17][18][19][20][21][22][23][24] In cases with detailed descriptions, the clinical diagnoses were FTLD in 14 cases, progressive non-fluent aphasia in three cases, semantic dementia in one case, MND in five cases, PLS in three cases, Alzheimer's disease in four cases, PSP in six cases, multiple system atrophy one case, corticobasal syndrome (CBS) in two cases, and one case of Creutzfeldt-Jakob disease.…”

Section: Discussionmentioning

confidence: 99%

An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex

et al. 2018

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Globular glial tauopathy (GGT) is a 4-repeat (4R) tauopathy in which 4R tau accumulates to form globular glial inclusions (GGIs), predominantly in oligodendroglia. To date, little has been reported on iron deposits in patients with GGT. We report a case of GGT with iron deposits in a 78-year-old woman presenting with an 8-year history of slowly progressing limb weakness and cognitive decline. Susceptibility-weighted imaging revealed a low signal intensity in the right precentral gyrus, suggesting iron deposition. A clinical diagnosis of motor neuron disease with dementia was made 4 years after onset. At autopsy, gross pathological findings showed atrophy of the frontal and temporal lobes. A localized area of the precentral gyrus corresponding to the most severely affected limb showed the strongest atrophy, macroscopically, and displayed 4R tau-immunoreactive GGIs and microscopically many ferritin-immunoreactive neurons. We diagnosed this patient as having GGT. This is the first GGT case with iron deposition confirmed both radiologically and pathologically.

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Temporal Variant Frontotemporal Dementia Is Associated with Globular Glial Tauopathy

Abstract: Supplemental Digital Content is available in the text.

Cited by 20 publications

References 15 publications

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) due to microtubule‐associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) due to microtubule‐associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy

Typical and atypical pathology in primary progressive aphasia variants

An autopsy case of globular glial tauopathy presenting with clinical features of motor neuron disease with dementia and iron deposition in the motor cortex

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