Spreading of tau pathology in <scp>A</scp>lzheimer's disease by cell‐to‐cell transmission

Mohamed, Nguyen‐Vi; Herrou, Thibaut; Plouffe, Vanessa; Piperno, Nicolas; Leclerc, Nicole

doi:10.1111/ejn.12229

Cited by 105 publications

(91 citation statements)

References 101 publications

(168 reference statements)

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“…In AD, NFTs are prominent early in entorhinal cortex and later appear in anatomically connected brain regions (Braak and Braak, 1995). Cell to cell transmission is one hypothesis accounting for this phenomenon (Mohamed et al, 2013). Previous studies suggest that certain forms of tau released into the extracellular space can enter cells and induce further tau aggregation (Clavaguera et al, 2009;Frost et al, 2009;Guo and Lee, 2011;Kfoury et al, 2012;Iba et al, 2013).…”

Section: Brief Definitive Reportmentioning

confidence: 99%

Neuronal activity regulates extracellular tau in vivo

Yamada¹,

Holth²,

Liao³

et al. 2014

J Cell Biol

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Tau is primarily a cytoplasmic protein that stabilizes microtubules. However, it is also found in the extracellular space of the brain at appreciable concentrations. Although its presence there may be relevant to the intercellular spread of tau pathology, the cellular mechanisms regulating tau release into the extracellular space are not well understood. To test this in the context of neuronal networks in vivo, we used in vivo microdialysis. Increasing neuronal activity rapidly increased the steady-state levels of extracellular tau in vivo. Importantly, presynaptic glutamate release is sufficient to drive tau release. Although tau release occurred within hours in response to neuronal activity, the elimination rate of tau from the extracellular compartment and the brain is slow (half-life of 11 d). The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself.

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Section: Brief Definitive Reportmentioning

confidence: 99%

Neuronal activity regulates extracellular tau in vivo

Yamada¹,

Holth²,

Liao³

et al. 2014

J Cell Biol

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“…Tau is constitutively released from neurons under physiological conditions [71,[76][77][78][79][80][81][82][83][84][85][86][87][88]. The secretion is multifaceted, involving diverse intracellular components such as autophagosomes, Golgi, endosomes, ectosomes, lysosomes, microsomes and endoplasmic reticulum [89].…”

Section: Mechanisms Of Tau Release and Spreadingmentioning

confidence: 99%

Transmission of Tau Pathology from Human to Rodent Brain: How to Humanise Animal Models for Alzheimer’s Disease Research

Smolek¹,

Jadhav²,

Valachova³

et al. 2017

J Alzheimers Dis Parkinsonism

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“…Somewhat concerning are the studies suggesting protein templating with trans-synaptic transmission 44 and the incorporation of the tauopathies in the lexicon of prion (or prion-like) diseases. Transgenic mice overexpressing P301L tau in the entorhinal cortex, for example, demonstrate de novo wild-type ptau in brain regions synaptically connected with the performant pathway.…”

Section: Cte As a Prion Diseasementioning

confidence: 99%

Chronic traumatic encephalopathy: A paradigm in search of evidence?

Castellani

2015

Laboratory Investigation

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Chronic traumatic encephalopathy (CTE) has been in the medical literature since the 1920s. It is characterized clinically by diverse neuropsychiatric symptoms, and pathologically by variable degrees of phosphorylated tau accumulation in the brain. The evolving paradigm for the pathogenesis of CTE suggests that concussion or subconcussion from athletic participation initiates a cascade of pathologic events, encompassing neuroinflammation and protein templating with trans-synaptic neurotoxicity. The end result is neurologic and neurobehavioral deterioration, often with self-harm. Although these concepts warrant further investigation, the available evidence permits no conclusions as regards the pathogenesis of the reported findings. Investigations into the role of premorbid or co-morbid neurodegenerative diseases has been limited to date, and in-depth genetic analyses have not been performed. The role of concussion or subconcussion if any, whether and how the condition progresses over time, the extent of phosphorylated tau in clinically normal athletes, the role of phosphorylated tau as a toxic species versus an inert disease response, and whether protein templating has any in vivo relevance remain to be elucidated.

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Spreading of tau pathology in Alzheimer's disease by cell‐to‐cell transmission

Cited by 105 publications

References 101 publications

Neuronal activity regulates extracellular tau in vivo

Neuronal activity regulates extracellular tau in vivo

Transmission of Tau Pathology from Human to Rodent Brain: How to Humanise Animal Models for Alzheimer’s Disease Research

Chronic traumatic encephalopathy: A paradigm in search of evidence?

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