The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies in Subcortical Nuclei and Progression of Argyrophilic Grain Disease

Yokota, Osamu; Nagao, Shigeto; Ishizu, Hideki; Oshima, Etsuko; Hasegawa, Masato; Okahisa, Yuko; Terada, Seishi; Yamada, Norihito

doi:10.1111/bpa.12319

Cited by 24 publications

(60 citation statements)

References 53 publications

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“…In our study, we explored astrocytic lesions in the superior frontal cortex, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra, oculomotor nucleus, pontine nucleus, inferior olivary nucleus and cerebellar dentate nucleus in 20 AGD cases using Gallyas method and AT8 immunohistochemistry. In our original report, the term “Gallyas‐negative tau‐positive tufted astrocyte‐like astrocytic inclusions” was used to refer to “granular/fuzzy astrocytes” proposed later by Kovacs et al Indeed, we confirmed that all of the Gallyas‐negative tau‐positive tufted astrocyte‐like astrocytic inclusions in AGD cases examined previously were actually granular/fuzzy astrocytes in re‐evaluation. Therefore, we used the term granular/fuzzy astrocytes in this paper.…”

Section: Pathological Relationship Between Agd and Psp Pathologysupporting

confidence: 75%

“…In 19 AGD cases that we examined, the Braak stage of 3R tau‐positive NFTs was not significantly correlated with the Saito AGD stage . Given these findings, 3R tau‐positive NFTs may be independent of the pathophysiology of AGD …”

Section: Pathological Features In Agdmentioning

confidence: 99%

“…Although tufted astrocytes are pathological hallmarks of PSP, we recently reported that some AGD cases had a small number of Gallyas‐positive tau‐positive tufted astrocytes (Figs j,e–h,m–p), even when AGD cases did not have sufficient NFTs to fulfill the pathological criteria of PSP . In our study, we explored astrocytic lesions in the superior frontal cortex, caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra, oculomotor nucleus, pontine nucleus, inferior olivary nucleus and cerebellar dentate nucleus in 20 AGD cases using Gallyas method and AT8 immunohistochemistry.…”

Section: Pathological Relationship Between Agd and Psp Pathologymentioning

confidence: 99%

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Neuropathological comorbidity associated with argyrophilic grain disease

et al. 2017

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Argyrophilic grain disease (AGD) is a common fourrepeat tauopathy in elderly people. While dementia is a major clinical picture of AGD, recent studies support the possibility that AGD may be a pathological base in some patients with mild cognitive impairment, late-onset psychosis, bipolar disorder and depression. AGD often coexists with various other degenerative changes. The frequency of AGD in progressive supranuclear palsy (PSP) cases was reported to range from 18.8% to 80%. The frequency of AGD in corticobasal degeneration (CBD) cases tends to be higher than that in PSP cases, ranging from 41.2% to 100%. Conversely, in our previous study of the frequencies of mild PSP and CBD pathologies in AGD cases, five of 20 AGD cases (25%) had a few Gallyaspositive tufted astrocytes, six cases (30%) had a few granular/fuzzy astrocytes, and one case (5.0%) had a few Gallyas-positive astrocytic plaques in the putamen, caudate nucleus and/or superior frontal gyrus. Both Gallyaspositive tufted astrocytes and Gallyas-negative tau-positive granular/fuzzy astrocytes preferentially developed in the putamen, caudate nucleus and superior frontal cortex in AGD cases, being consistent with the predilection sites of Gallyas-positive tufted astrocytes in PSP cases. Further, in AGD cases, the quantities of Gallyas-positive tufted astrocytes, overall tau-positive astrocytes, and tau-positive neurons in the subcortical nuclei and superior frontal cortex were significantly correlated with Saito AGD stage, respectively. The frequency of AGD in AD cases was reported to reach up to 25% when using four-repeat tau immunohistochemistry.Pretangles are essential pathologies in AGD; however, the Braak stage of threerepeat tau-positive NFTs, which may indicate mild AD pathology or primary age-related tauopathy, was not correlated with Saito AGD stage. Clinicians should be aware of the possibility that coexisting AGD may impact clinical and radiological features in cases of other degenerative diseases.

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Section: Pathological Relationship Between Agd and Psp Pathologysupporting

confidence: 75%

Section: Pathological Features In Agdmentioning

confidence: 99%

Section: Pathological Relationship Between Agd and Psp Pathologymentioning

confidence: 99%

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Neuropathological comorbidity associated with argyrophilic grain disease

et al. 2017

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“…Muscle weakness develops only in 4R tau 151–391 rats[132, 331, 373, 542]Tau35E187-L44133–37Present in AGD, PSP, and CBD, but not control brainIncludes four microtubule binding repeats. Expression of Tau35 mice in transgenic mice induces tau pathology, cognitive and motor dysfunction[16, 42, 216, 520]Tau-CTF24L243-L4412420–28 kDa C-terminal tau species detected in AD, CBD, PSP, and FTLD-tau, but not control brainIncludes four microtubule binding repeats. Present in Tg601 mice which exhibit increased tau phosphorylation and synapse loss[327]

Tau fragments that have been detected in human brain that is potentially associated with the development of tauopathy.

…”

Section: Tau-mediated Neurodegenerationmentioning

confidence: 99%

Roles of tau protein in health and disease

2017

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Tau is well established as a microtubule-associated protein in neurons. However, under pathological conditions, aberrant assembly of tau into insoluble aggregates is accompanied by synaptic dysfunction and neural cell death in a range of neurodegenerative disorders, collectively referred to as tauopathies. Recent advances in our understanding of the multiple functions and different locations of tau inside and outside neurons have revealed novel insights into its importance in a diverse range of molecular pathways including cell signalling, synaptic plasticity, and regulation of genomic stability. The present review describes the physiological and pathophysiological properties of tau and how these relate to its distribution and functions in neurons. We highlight the post-translational modifications of tau, which are pivotal in defining and modulating tau localisation and its roles in health and disease. We include discussion of other pathologically relevant changes in tau, including mutation and aggregation, and how these aspects impinge on the propensity of tau to propagate, and potentially drive neuronal loss, in diseased brain. Finally, we describe the cascade of pathological events that may be driven by tau dysfunction, including impaired axonal transport, alterations in synapse and mitochondrial function, activation of the unfolded protein response and defective protein degradation. It is important to fully understand the range of neuronal functions attributed to tau, since this will provide vital information on its involvement in the development and pathogenesis of disease. Such knowledge will enable determination of which critical molecular pathways should be targeted by potential therapeutic agents developed for the treatment of tauopathies.

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“…For example, in AGD brains, argyrophilic grains are most sensitively demonstrated by AT8 immunohistochemistry, followed by RD4 immunohistochemistry, and then the Gallyas method . Likewise, the number of tau‐positive astrocytic lesions is larger than the number of Gallyas‐positive astrocytic lesions threads, and in some tau‐positive astrocytic lesions, various proportions of astrocytic threads are stained by the Gallyas method . Thus, all 4R tau‐positive lesions are not always stained with the Gallyas method.…”

Section: Discussionmentioning

confidence: 76%

Pick's disease with neuronal four‐repeat tau accumulation in the basal ganglia, brain stem nuclei and cerebellum

et al. 2017

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It is very rare that cases of Pick's disease, a representative three-repeat (3R) tauopathy, also have significant four-repeat (4R) tau accumulation. Here, we report a Pick's disease case that clinically showed behavioral variant frontotemporal dementia without motor disturbance during the course, and pathologically had 3R tau-positive Pick bodies as well as numerous 4R tau-positive neuronal cytoplasmic inclusions (NCIs). Abundant 3R tau-positive 4R tau-negative spherical or horseshoe-shaped Pick bodies were found in the frontotemporal cortex, limbic region, striatum and pontine nucleus. On the other hand, many 4R tau-positive, 3R tau-negative, Gallyas-negative dot-, rod- or intertwined skein-like NCIs were found mainly in the subthalamic nucleus, pontine nucleus, inferior olivary nucleus and cerebellar dentate nucleus. Tufted astrocytes, astrocytic plaques, argyrophilic grains or globular glial inclusions were absent. Double-labeling immunofluorescence demonstrated that 3R tau was hardly accumulated in 4R tau-positive inclusions. On tau immunoblotting, while 60 and 64 kDa bands were demonstrated in the frontal cortex, 60, 64 and 68 kDa bands, as well as the 33 kDa tau fragments that are reported to be characteristic of progressive supranuclear palsy brains, were found in the basal ganglia and cerebellum. No mutation was identified in the tau gene. The present case suggests that, although probably rare, some Pick's disease cases have non-negligible 4R tau pathology in the subcortical nuclei, and that such 4R tau pathology can affect the evaluation of the distribution of AT8-positive tau pathology in Pick's disease cases.

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The Relationship Between Development of Neuronal and Astrocytic Tau Pathologies in Subcortical Nuclei and Progression of Argyrophilic Grain Disease

Cited by 24 publications

References 53 publications

Neuropathological comorbidity associated with argyrophilic grain disease

Neuropathological comorbidity associated with argyrophilic grain disease

Roles of tau protein in health and disease

Pick's disease with neuronal four‐repeat tau accumulation in the basal ganglia, brain stem nuclei and cerebellum

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