Progressive Supranuclear Palsy and Corticobasal Degeneration

Dickson, Dennis W.; Hauw, J J; Agid, Yves; Litvan, Irene

doi:10.1002/9781444341256.ch15

Cited by 42 publications

(44 citation statements)

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“…Both the subcortical and cortical regions identified in this study do typically show neurodegeneration and tau pathology at autopsy 2, 25 . However, we must be cautious in the pathological interpretation of these tau-PET findings.…”

Section: Discussionmentioning

confidence: 58%

“…Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy characterized by the deposition of 4-repeat (4R) tau in globose neurofibrillary tangles, tufted astrocytes, coiled bodies and threads that are found in basal ganglia, diencephalon, brainstem and motor and premotor cortex 1, 2 . The most common clinical phenotype associated with PSP is Richardson’s syndrome, characterized by difficulty with gait and postural instability, frequent falls, and abnormal eye movements (vertical supranuclear gaze palsy) 3, 4 .…”

Section: Introductionmentioning

confidence: 99%

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[¹⁸F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

et al. 2016

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Background The [18F]AV-1451 positron emission tomography ligand allows the in-vivo assessment of tau proteins in the brain. It shows strong binding in Alzheimer’s dementia but little is known about how it performs in progressive supranuclear palsy, a primary 4R tauopathy. Objectives To determine whether [18F]AV-1451 uptake can be observed in progressive supranuclear palsy and to characterize the regional distribution compared to controls and Alzheimer’s dementia. Methods [18F]AV-1451 positron emission tomography was performed in ten patients with probable progressive supranuclear palsy. These patients were age and gender-matched to 50 controls and ten Alzheimer’s dementia patients that had undergone identical [18F]AV-1451 imaging. Regional comparisons of [18F]AV-1451 uptake were performed across the whole brain using region-of-interest and voxel-level analyses, and correlations between regional [18F]AV-1451 and the progressive supranuclear palsy rating scale were assessed. Results An elevated [18F]AV-1451 signal was observed in progressive supranuclear palsy compared to controls in pallidum, midbrain, dentate nucleus of the cerebellum, thalamus, caudate nucleus, and frontal regions. Signal in the cerebellar dentate and pallidum were also greater in progressive supranuclear palsy compared to Alzheimer’s dementia. Conversely, [18F]AV-1451 signal across the cortex was higher in Alzheimer’s dementia compared to progressive supranuclear palsy. [18F]AV-1451 signal in a number of regions correlated with the progressive supranuclear palsy rating scale. Conclusions Progressive supranuclear palsy is associated with elevated [18F]AV-1451 signal in a characteristic and distinct regional pattern that correlates with disease severity and differs from the patterns observed in Alzheimer’s dementia.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

[¹⁸F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

et al. 2016

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“…These characteristic features help GGT to be distinguished from other 4R-tauopathies, in particular PSP. Whether the neuropathological subtypes of GGT are distinct disease entities or part of a spectrum of disease is open to a similar debate that has been on-going for PSP and CBD [5]. The severe involvement of oligodendroglia and resulting white matter changes (myelin pallor, axonal loss and gliosis) suggests that GGT expands the spectrum of primary oligodendrogliopathies.…”

Section: Resultsmentioning

confidence: 99%

“…1), the use of Gallyas silver-staining [8] could prove instrumental as a diagnostic tool to help distinguish GGT from PSP, especially in the evaluation of astrocytic pathology, although occasional Gallyas-positive tufted astrocyte-like inclusions may be noted in GGT cases as well. The neuropathological features of GGT should be easily distinguishable from those of CBD and AGD [5, 25]; however, this is not the case for FTLD– MAPT , which can share neuropathological and biochemical similarities with GGT [9, 11] (Table 2). For these reasons, suspected GGT cases should be routinely sent for MAPT genetic analysis to exclude the diagnosis of FTLD– MAPT .…”

Section: Future Classification and Nosologymentioning

confidence: 99%

Globular glial tauopathies (GGT): consensus recommendations

Bigio²,

et al. 2013

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Rrecent studies have highlighted a group of 4-repeat (4R) tauopathies that are characterised neuropathologically by widespread, globular glial inclusions (GGIs). Tau immunohistochemistry reveals 4R immunore-active globular oligodendroglial and astrocytic inclusions and the latter are predominantly negative for Gallyas silver staining. These cases are associated with a range of clinical presentations, which correlate with the severity and distribution of underlying tau pathology and neurodegeneration. Their heterogeneous clinicopathological features combined with their rarity and under-recognition have led to cases characterised by GGIs being described in the literature using various and redundant terminologies. In this report, a group of neuropathologists form a consensus on the terminology and classification of cases with GGIs. After studying microscopic images from previously reported cases with suspected GGIs (n = 22), this panel of neuropathologists with extensive experience in the diagnosis of neurodegenerative diseases and a documented record of previous experience with at least one case with GGIs, agreed that (1) GGIs were present in all the cases reviewed; (2) the morphology of globular astrocytic inclusions was different to tufted astrocytes and finally that (3) the cases represented a number of different neuropathological subtypes. They also agreed that the different morphological subtypes are likely to be part of a spectrum of a distinct disease entity, for which they recommend that the overarching term globular glial tauopathy (GGT) should be used. Type I cases typically present with frontotemporal dementia, which correlates with the fronto-temporal distribution of pathology. Type II cases are characterised by pyramidal features reflecting motor cortex involvement and corticospinal tract degeneration. Type III cases can present with a combination of frontotemporal dementia and motor neuron disease with fronto-temporal cortex, motor cortex and corticospinal tract being severely affected. extrapyramidal features can be present in Type II and III cases and significant degeneration of the white matter is a feature of all GGT subtypes. Improved detection and classification will be necessary for the establishment of neuropathological and clinical diagnostic research criteria in the future.

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“…In PSP, neurofibrillary tangles (NFT), neuropil threads (NTs) and tau-positive tufted astrocytes (TAs) are predominantly found in basal ganglia and brainstem, whereas in CBD pretangles, NTs and astrocytic plaques are found in gray and white matter of cortex, basal ganglia, diencephalon and rostral brainstem. 1 The classical clinical presentation of PSP is called PSP with Richardson’s syndrome (PSP-RS) and consists of an akinetic-rigid syndrome, supranuclear gaze palsy, cognitive impairment and falls. However, at least eight additional clinical types have been reported.…”

Section: Introductionmentioning

confidence: 99%

Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and corticobasal degeneration

et al. 2016

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BACKGROUND Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). Unexpectedly, tau pathology has been reported in a subset of LRRK2 mutation carriers. METHODS To estimate the frequency of pathogenic LRRK2 mutations, and to evaluate the association of common LRRK2 variants with risk of primary tauopathies, we studied 1039 progressive supranuclear palsy (PSP) and 145 corticobasal degeneration patients from the Mayo Clinic Florida brain bank and 1790 controls ascertained at Mayo Clinic. Sanger sequencing of LRRK2 exons 30, 31, 35 and 41 was performed in all patients and genotyping of all 17 known exonic variants with minor allele frequency >0.5% was performed in patients and controls. RESULTS LRRK2 mutational screening identified two known pathogenic mutations (p.G2019S and p.R1441C), each in one PSP patient, the novel p.A1413T mutation in a PSP patient and the rare p.R1707K mutation in a corticobasal degeneration patient. Both p.A1413T and p.R1707K mutations were predicted damaging by at least 2 of 3 prediction programs and affect evolutionary conserved sites of LRRK2. Association analysis using common LRRK2 variants only showed nominal association of the p.L153L variant with PSP. CONCLUSIONS Our study confirms the presence of pathogenic and potentially pathogenic LRRK2 mutations in pathologically confirmed primary tauopathies, albeit with low frequency. In contrast to PD, common LRRK2 variants do not appear to play a major role in determining PSP and corticobasal degeneration risk.

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Progressive Supranuclear Palsy and Corticobasal Degeneration

Cited by 42 publications

References 205 publications

[¹⁸F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

[¹⁸F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

Globular glial tauopathies (GGT): consensus recommendations

Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and corticobasal degeneration

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Progressive Supranuclear Palsy and Corticobasal Degeneration

Cited by 42 publications

References 205 publications

[18F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

[18F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

Globular glial tauopathies (GGT): consensus recommendations

Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and corticobasal degeneration

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[¹⁸F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy

[¹⁸F]AV‐1451 tau positron emission tomography in progressive supranuclear palsy