Association Between Globular Glial Tauopathies and Frontotemporal Dementia—Expanding the Spectrum of Gliocentric Disorders

Forrest, Shelley L.; Kril, Jillian J.; Kovács, Gábor G.

doi:10.1001/jamaneurol.2021.1813

Cited by 21 publications

(36 citation statements)

References 79 publications

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“…Neuropathological correlations are depicted in Figure 2. A particular pattern of GGT is the almost constant involvement of glial elements in the cerebral white matter [14]. Figure 2a-c…”

Section: Discussionmentioning

confidence: 95%

“…Neuropathological correlations are depicted in Figure 2 . A particular pattern of GGT is the almost constant involvement of glial elements in the cerebral white matter [ 14 ]. Figure 2a–c compares deposits of hyperphosphorylated tau protein visualized using an immunohistochemical reaction with the AT8 antibody clone from the same area of subcortical white matter in all three patients.…”

Section: Discussionmentioning

confidence: 99%

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Corpus callosum hypersignals and focal atrophy: Neuroimaging findings in globular glial tauopathy type I

Keller

Kavkova

Matěj

et al. 2021

Euro J of Neurology

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Globular glial tauopathies (GGTs) have heterogeneous presentations [1]; little evidence regarding typical clinical and magnetic resonance imaging (MRI) presentations is available. We report MRI findings for three autopsy-confirmed GGT cases, two presenting clinically with atypical primary progressive aphasia (PPA) and one with corticobasal syndrome (CBS). ME THODSThe first case (previously published) was a 69-year-old man with a combination of two PPA subtypes (i.e., early nonfluentagrammatical and late semantic variant) and hippocampal amnesia [2]. He initially had mild anomia, without language comprehension impairment at the single word and sentence level. Progressively, he developed lexical retrieval problems, speech apraxia, and

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“…Neuropathological correlations are depicted in Figure 2. A particular pattern of GGT is the almost constant involvement of glial elements in the cerebral white matter [14]. Figure 2a-c…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Corpus callosum hypersignals and focal atrophy: Neuroimaging findings in globular glial tauopathy type I

Keller

Kavkova

Matěj

et al. 2021

Euro J of Neurology

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“…Progressive supranuclear palsy (PSP) syndrome was first described by Steele, Richardson, and Olszewski in 1964 as a distinct clinicopathological entity ( 41 ). Although typical PSP pathology with tufted astrocytes ( Table 1 ) is the most common underlying pathology of this clinical syndrome (PSP-RS), a small subset of patients with an underlying CBD pathology might present with RS (CBD-RS) and there are rare reports of GGT presenting with a PSP syndrome ( Figure 1 ) ( 34 , 42 ). Original description of RS included nine patients presenting with early and prominent supranuclear ophthalmoplegia, severe dysarthria, axial rigidity with extensor posturing of the neck, mild dementia, and pseudobulbar palsy with subsequent progression to a bedridden state and death in 5 to 7 years ( 41 ).…”

Section: Clinical Syndromes With Strong Association To a Primary Tauo...mentioning

confidence: 99%

“…Pathologic diagnoses are shown on the left and clinical syndromes on the right. Degree to which various pathologies contribute to a specific clinical phenotype is estimated based on available pathology-confirmed studies, including: PSP ( 20 – 23 ); CBD ( 23 – 27 ); AD ( 28 – 31 ); PiD ( 32 ); LBD ( 33 ); GGT ( 34 ); TDP ( 35 – 37 ); AGD ( 38 ); and PART ( 15 , 39 , 40 ). AD, Alzheimer's disease; AGD, argyrophilic grain disease; CBD, corticobasal degeneration; CBS corticobasal syndrome; FTD-MND, frontotemporal dementia-motor neuron disease; GGT, globular glial tauopathy; LBD, Lewy body disease; LOCA, late onset cerebellar ataxia; lvPPA logopenic variant primary progressive aphasia; MND, motor neuron disease; nfaPPA, non-fluent agrammatic primary progressive aphasia; PAGF, progressive akinesia and gait freezing; PART, primary age-related tauopathy; PCA, posterior cortical atrophy; PiD, Pick's disease; PSP, progressive supranuclear palsy; svPPA, semantic variant primary progressive aphasia; TDP, transactive response DNA binding protein 43 kDa pathology.…”

Section: Introductionmentioning

confidence: 99%

Clinical Spectrum of Tauopathies

2022

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Tauopathies are both clinical and pathological heterogeneous disorders characterized by neuronal and/or glial accumulation of misfolded tau protein. It is now well understood that every pathologic tauopathy may present with various clinical phenotypes based on the primary site of involvement and the spread and distribution of the pathology in the nervous system making clinicopathological correlation more and more challenging. The clinical spectrum of tauopathies includes syndromes with a strong association with an underlying primary tauopathy, including Richardson syndrome (RS), corticobasal syndrome (CBS), non-fluent agrammatic primary progressive aphasia (nfaPPA)/apraxia of speech, pure akinesia with gait freezing (PAGF), and behavioral variant frontotemporal dementia (bvFTD), or weak association with an underlying primary tauopathy, including Parkinsonian syndrome, late-onset cerebellar ataxia, primary lateral sclerosis, semantic variant PPA (svPPA), and amnestic syndrome. Here, we discuss clinical syndromes associated with various primary tauopathies and their distinguishing clinical features and new biomarkers becoming available to improve in vivo diagnosis. Although the typical phenotypic clinical presentations lead us to suspect specific underlying pathologies, it is still challenging to differentiate pathology accurately based on clinical findings due to large phenotypic overlaps. Larger pathology-confirmed studies to validate the use of different biomarkers and prospective longitudinal cohorts evaluating detailed clinical, biofluid, and imaging protocols in subjects presenting with heterogenous phenotypes reflecting a variety of suspected underlying pathologies are fundamental for a better understanding of the clinicopathological correlations.

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“…Astrocytes provide homeostatic control at all levels of organisation in the central nervous system including the regulation of ionic and neurotransmitter homeostasis, providing energy substrates to surrounding neurons, modulating synaptic transmission, secretion of trophic factors, maintenance of the blood-brain-barrier, and reacting to local insults and in ammation [2,5]. Furthermore, there is evidence of the important role of astrocytes in the pathogenesis of a range of neurological conditions [6-8], including neurodegenerative diseases, and their involvement in brain ageing [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Distribution patterns of astrocyte populations in the human cortex

Forrest

Kim

Crockford

et al. 2022

Preprint

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Astrocytes are a major class of glial cell in the central nervous system that have a diverse range of types and functions thought to be based on their anatomical location, morphology and cellular properties. Recent studies highlight that astrocyte dysfunction contributes to the pathogenesis of neurological conditions. However, few studies have described the pattern, distribution and density of astrocytes in the adult human cortex. This study mapped the distribution and density of astrocytes immunolabelled with a range of cytoskeletal and membrane markers in the human frontal cortex. Distinct and overlapping astrocyte populations were determined. The frontal cortex from ten normal control cases (75±9 years) was immunostained with glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase-1 L1 (ALDH1L1), connexin-43 (Cx43), aquaporin-4 (AQP4), and glutamate transporter 1 (GLT-1). All markers labelled populations of astrocytes in the grey and white matter, separate cortical layers, subpial and perivascular regions. All markers were informative for labelling different cellular properties and cellular compartments of astrocytes. ALDH1L1 labelled the largest population of astrocytes, and Cx43-immunopositive astrocytes were found in all cortical layers. AQP4 and GLT-1 labelled distal astrocytic process and end-feet in the same population of astrocytes (98% of GLT-1-immunopositive astrocytes contained AQP4). This study highlights the diversity of astrocytes in the human cortex, providing a reference map of the distribution of distinct and overlapping astrocyte populations which can be used for comparative purposes in various disease, inflammatory and injury states involving astrocytes.

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Association Between Globular Glial Tauopathies and Frontotemporal Dementia—Expanding the Spectrum of Gliocentric Disorders

Cited by 21 publications

References 79 publications

Corpus callosum hypersignals and focal atrophy: Neuroimaging findings in globular glial tauopathy type I

Corpus callosum hypersignals and focal atrophy: Neuroimaging findings in globular glial tauopathy type I

Clinical Spectrum of Tauopathies

Distribution patterns of astrocyte populations in the human cortex

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