Familial parkinsonism and dementia with ballooned neurons, argyrophilic neuronal inclusions, atypical neurofibrillary tangles, tau-negative astrocytic fibrillary tangles, and Lewy bodies

Mizutani, Tetsuya; Inose, Tomoko; Nakajima, Shinji; Kakimi, Shigeo; Uchigata, Masanobu; Ikeda, Kenji; Takasu, Toshiaki

doi:10.1007/s004010050761

Cited by 28 publications

(24 citation statements)

References 45 publications

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“…An additional feature was the presence of GCI-like oligodendroglial inclusions with a distribution similar to that found in MSA. This case shows some similarity to reports of A53T mutation and multiplication of SNCA (Table 2) and also to a Japanese kindred reported in an abstract as carrying a G51D SNCA mutation, but without detailed segregation data [50, 51]. However, features including dense accumulation of α-synuclein-positive inclusions in the striatum and very severe neocortical α-synuclein pathology affecting both superficial and deep cortical laminae distinguish this case from other reported cases with SNCA mutations.…”

Section: Discussionsupporting

confidence: 84%

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy?

Kiely

Asi

Kara³

et al. 2013

Acta Neuropathol

380

318

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We report a British family with young-onset Parkinson’s disease (PD) and a G51D SNCA mutation that segregates with the disease. Family history was consistent with autosomal dominant inheritance as both the father and sister of the proband developed levodopa-responsive parkinsonism with onset in their late thirties. Clinical features show similarity to those seen in families with SNCA triplication and to cases of A53T SNCA mutation. Post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes in addition to the caudate, putamen, globus pallidus and amygdala. There was severe loss of pigmentation in the substantia nigra and pallor of the locus coeruleus. Neuronal loss was most marked in frontal and temporal cortices, hippocampal CA2/3 subregions, substantia nigra, locus coeruleus and dorsal motor nucleus of the vagus. The cellular pathology included widespread and frequent neuronal α-synuclein immunoreactive inclusions of variable morphology and oligodendroglial inclusions similar to the glial cytoplasmic inclusions of multiple system atrophy (MSA). Both inclusion types were ubiquitin and p62 positive and were labelled with phosphorylation-dependent anti-α-synuclein antibodies In addition, TDP-43 immunoreactive inclusions were observed in limbic regions and in the striatum. Together the data show clinical and neuropathological similarities to both the A53T SNCA mutation and multiplication cases. The cellular neuropathological features of this case share some characteristics of both PD and MSA with additional unique striatal and neocortical pathology. Greater understanding of the disease mechanism underlying the G51D mutation could aid in understanding of α-synuclein biology and its impact on disease phenotype.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-013-1096-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 84%

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy?

Kiely

Asi

Kara³

et al. 2013

Acta Neuropathol

380

318

View full text Add to dashboard Cite

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“…These latest results may provide additional evidence in favor of a link between GVD and AD. Another argument against GVD as an AD-related pathology is that vacuolar lesions in ballooned neurons have been described previously as GVD in a familial PD case [30]. Nonetheless, this study did not take into account that CK1d and CK1e failed to stain GVD within ballooned neurons in our CBD and AGD cases as well as in the sample reported by Schwab et al [35].…”

Section: Discussioncontrasting

confidence: 47%

Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response

et al. 2011

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Granulovacuolar degeneration (GVD) is characterized by the presence of vacuolar cytoplasmic lesions in nerve cells of the medial temporal lobe. These changes occur in older non-diseased individuals as well as in patients with Alzheimer's disease (AD), progressive supranuclear palsy (PSP), Pick's, sporadic Parkinson's (PD), and Guam diseases. We stained representative paraffin sections from all parts of the brain with anti-pTDP43, anti-CK1d or anti-CK1e from 14 non-demented elderly, 19 AD, 17 non-AD tauopathy, 9 sporadic PD, and 5 TDP43-proteinopathy [amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD)] cases. Our results showed five stages of GVD based on its distribution pattern: GVD began in the hippocampal subfields CA1, CA2, and the subiculum. In a second stage, entorhinal cortex, and CA4 neurons exhibited GVD. Additional neurons were involved in the temporal neocortex in stage 3, whereas the affection of the amygdala and/or the hypothalamus marked stage 4. A fifth and final stage was characterized by additional GVD in the cingulate cortex and occasionally in the frontal and parietal cortices as well as in the oral raphe and pedunculopontine tegmental nuclei. The GVD stages correlated with neurofibrillary tangle stages, Consortium to Establish a Registry for AD (CERAD) scores for neuritic plaque pathology, amyloid b-protein deposition phases, cerebral amyloid angiopathy stages, and clinical dementia rating (CDR) scores. No associations were seen between GVD stage and the presence of non-AD tauopathies, PD, ALS, or FTLD cases. In conclusion, GVD affects neurons in a hierarchical sequence that allows the distinction of five stages. The topographic distribution of GVD restricted to regions involved in response to chronic stress could indicate a link between GVD and chronically stressful influences. Moreover, the association of the GVD stages with those of AD-related pathology but not with other neurodegenerative disorders points to a possible role of GVD and the response to chronic stress in the pathogenesis of AD.

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“…The precise role of Bc in the development and progression of this disease is still unknown, despite the findings that the disease is characterised by 'ballooned' neurons [195] which express Bc [105]. Both PD and Huntington's disease are intracellular protein aggregation diseases, like CJD.…”

Section: The Role Of Shsps In Neurodegenerative Diseasementioning

confidence: 99%

Small heat-shock proteins: important players in regulating cellular proteostasis

Treweek

Meehan

Ecroyd

et al. 2014

Cell. Mol. Life Sci.

175

177

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Small heat-shock proteins (sHsps) are a diverse family of intra-cellular molecular chaperone proteins that play a critical role in mitigating and preventing protein aggregation under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) thereby avoiding the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. Significant progress has been made of late in understanding the structure and chaperone mechanism of sHsps. In this review, we discuss some of these advances, with a focus on mammalian sHsp hetero-oligomerisation, the mechanism by which sHsps act as molecular chaperones to prevent both amorphous and fibrillar protein aggregation, and the role of posttranslational modifications in sHsp chaperone function, particularly in the context of disease. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Abstract (word count = 159)Small heat-shock proteins (sHsps) are a diverse family of intracellular molecular chaperone proteins that play a critical role in preventing protein unfolding, misfolding and aggregation, particularly under stress conditions such as elevated temperature, oxidation and infection. In doing so, they assist in the maintenance of protein homeostasis (proteostasis) and thereby avoid the deleterious effects that result from loss of protein function and/or protein aggregation. The chaperone properties of sHsps are therefore employed extensively in many tissues to prevent the development of diseases associated with protein aggregation. There has been much research into the structure and mechanism of chaperone action of sHsps over approximately the past 30 years, and significant progress has been made of late, however, there are still many unanswered questions relating to these aspects of sHsps. In this review, we outline some of the recent advances in understanding the structure and function of mammalian sHsps, particularly in the context of their many and varied roles in disease.

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Familial parkinsonism and dementia with ballooned neurons, argyrophilic neuronal inclusions, atypical neurofibrillary tangles, tau-negative astrocytic fibrillary tangles, and Lewy bodies

Cited by 28 publications

References 45 publications

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy?

α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson’s disease and multiple system atrophy?

Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response

Small heat-shock proteins: important players in regulating cellular proteostasis

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