Tauopathy in human and experimental variant Creutzfeldt-Jakob disease

Giaccone, Giorgio; Mangieri, Michela; Capobianco, Raffaella; Limido, Lucia; Hauw, J. J.; Haı̈k, Stéphane; Fociani, Paolo; Bugiani, Orso; Tagliavini, Fabrizio

doi:10.1016/j.neurobiolaging.2007.04.026

Cited by 52 publications

(56 citation statements)

References 45 publications

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“…The third hypothesis is supported by the occurrence of Tau pathology in different types of cerebral amyloidosis (Holton et al ., 2001; Giaccone et al ., 2008). …”

Section: Introductionmentioning

confidence: 99%

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

et al. 2016

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SummaryThe mechanistic relationship between amyloid β1‐42 (Aβ1‐42) and the alteration of Tau protein are debated. We investigated the effect of Aβ1‐42 monomers and oligomers on Tau, using mice expressing wild‐type human Tau that do not spontaneously develop Tau pathology. After intraventricular injection of Aβ1‐42, mice were sacrificed after 3 h or 4 days. The short‐lasting treatment with Aβ monomers, but not oligomers, showed a conformational PHF‐like change of Tau, together with hyperphosphorylation. The same treatment induced increase in concentration of GSK3 and MAP kinases. The inhibition of the kinases rescued the Tau changes. Aβ monomers increased the levels of total Tau, through the inhibition of proteasomal degradation. Aβ oligomers reproduced all the aforementioned alterations only after 4 days of treatment. It is known that Aβ1‐42 monomers foster synaptic activity. Our results suggest that Aβ monomers physiologically favor Tau activity and dendritic sprouting, whereas their excess causes Tau pathology. Moreover, our study indicates that anti‐Aβ therapies should be targeted to Aβ1‐42 monomers too.

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“…The third hypothesis is supported by the occurrence of Tau pathology in different types of cerebral amyloidosis (Holton et al ., 2001; Giaccone et al ., 2008). …”

Section: Introductionmentioning

confidence: 99%

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

et al. 2016

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“…Rarely, tauopathy has also been described in GSS linked with the P102L mutation [37] as in the case with P102L-129V in the present study. Tauopathy may also occur in human and experimental variants of Creutzfeldt-Jakob disease [38,39]. Certain GSS, similar to that seen in AD [53].…”

Section: Discussionmentioning

confidence: 91%

Gerstmann-Straüssler-Scheinker PRNP P102L-129V mutation

Ferrer

Carmona

Blanco

et al. 2011

Translational Neuroscience

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Neuropathological and biochemical studies in a case of Gerstmann-Straüssler-Scheinker disease bearing the PRNP P102L-129V mutation showed numerous multicentric PrP res in the cerebral cortex, striatum, thalamus and cerebellum, PrP res globular deposits in the anterior and posterior horns of the spinal cord, and multiple granular PrP res deposits in the grey and white matter of the encephalon and spinal cord. Western blots with antiPrP res antibodies revealed several weak bands ranging from 36 to 66 kDa, weak bands of 29 and 24 kDa, a strong band of about 20 kDa, a low band of molecular weight around 15 kDa and a weaker band of about 7 kDa. Spongiform degeneration was absent. Hyper-phosphorylated 3R and 4R tau occurred in dystrophic neurites surrounding PrP res plaques, neuropil threads and, to a lesser degree, in the form of neurofibrillary tangles. Gel electrophoresis of sarkosyl-insoluble fractions and western blotting with anti-phospho-tau antibodies showed a pattern similar to that seen in Alzheimer disease cases run in parallel. Dystrophic neurites in the vicinity of PrP res plaques were enriched in voltage dependent anion channel thus suggesting abnormal accumulation of mitochondria. These changes were associated with increased oxidative damage in neurons and astrocytes, Finally, increased expression of active stress kinases, that have the capacity to phosphorylate tau in vitro, p38 (p-38-P) and SAPK/ JNK (SAPK/JNK-P) was found in cell processes surrounding PrP plaques. Together, these observations provide evidences of mitochondrial abnormalities, and increased oxidative stress damage and oxidative stress responses in GSS bearing the PRNP P102L-129V mutation.

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Section: Insights Into "Prionoid" Lesion Propagation Mechanisms From mentioning

confidence: 99%

“…[10][11][12] This has raised the question of whether aggregation-prone proteins such as Asyn, Abeta and most recently tau, 13 that have established roles in neurodegenerative disease cytopathogenesis, may also participate in interneuronal lesion propagation. 14 The prion-like characteristics of Asyn and Abeta have been reviewed extensively in references 13 and 15-18; this review will focus on the qualifications of tau as a prion-especially in the context of recent findings from our lab and elsewhere suggesting that tau secretion and interneuronal transfer may play a material role in the biogenesis of CSF tau and lesion propagation in AD.…”

Section: Insights Into "Prionoid" Lesion Propagation Mechanisms From mentioning

confidence: 99%

Is tau ready for admission to the prion club?

Hall

Patuto

2012

Prion

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A ggregation-prone proteins associated with neurodegenerative disease, such as α-synuclein and β-amyloid, now appear to share key prion-like features with mammalian prion protein, such as the ability to recruit normal proteins to aggregates and to translocate between neurons. These features may shed light on the genesis of stereotyped lesion development patterns in conditions such as Alzheimer disease and Lewy body dementia. We discuss the qualifications of tau protein as a possible "prionoid" mediator of lesion spread based on recent characterizations of the secretion, uptake and transneuronal transfer of human tau isoforms in a variety of tauopathy models, and in human patients. In particular, we consider (1) the possibility that prionoid behavior of misprocessed tau in neurodegenerative disease may involve other aggregation-prone proteins, including PrP itself and (2) whether "prionlike" tau lesion propagation might include mechanisms other than protein-protein templating. Prions and TSEs as a General Model for Neurodegenerative DiseaseThe formation of abnormal protein aggregates provides a common element in the pathogenesis of the vast majority of neurodegenerative diseases in humans, including Alzheimer disease (AD), non-AD tauopathies, α-synucleinopathies such as Lewy body dementia, transmissible spongiform encephalopathies (TSEs), trinucleotide repeat diseases and amyotrophic lateral sclerosis. Since aggregate formation is generally considered (and has been modeled) as a cell-autonomous Is tau ready for admission to the prion club?Garth F. Hall* and Brian A. PatutoDepartment of Biological Sciences; University of Massachusetts Lowell; Lowell, MA USA process, investigations into the pathogenesis of most neurodegenerative diseases have until very recently focused on cytotoxicity mechanisms associated with aggregate formation. As a consequence, intercellular aspects of most neurodegenerative diseases have been relatively neglected until very recently, and remain poorly understood. An exception to this pattern has been the study of TSEs, in which the consequences of prion protein (PrP) misfolding were addressed at the organismal level years before meaningful studies of cellular mechanisms could be attempted. This is because the transmissability and bizarre epidemiology of these diseases made a basic understanding of the transmission mechanism prerequisite to any meaningful studies of TSE cytopathogenesis. However, during the 1980s and 1990s, PrP was progressively established as the necessary and sufficient agent for TSE transmission via the promulgation, systematic testing and validation of the "Prion Hypothesis." [1][2][3] Since then, the study of PrP biology and pathobiology at the molecular, cellular and organismal levels has led to a deepening appreciation of the subtlety with which specific misfolded conformers of PrP can reproduce and propagate disease-specific properties that define specific TSEs. Investigators have recently begun to use PrP propagation in TSEs as a model to address interneuronal aspect...

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Tauopathy in human and experimental variant Creutzfeldt-Jakob disease

Cited by 52 publications

References 45 publications

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

Beta‐amyloid 1‐42 monomers, but not oligomers, produce PHF ‐like conformation of Tau protein

Gerstmann-Straüssler-Scheinker PRNP P102L-129V mutation

Is tau ready for admission to the prion club?

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