P2‐533: Targeting phospho‐Ser422 by active Tau immunotherapy in THY‐Tau22, a suitable therapeutic approach

Troquier, Laetitia; Caillierez, Raphaëlle; Burnouf, Sylvie; Kervoaze, Gwenola; Grosjean, Marie-Eve; Zommer, Nadège; Sergeant, Nicolas; Lassalle, P.; Blum, David

doi:10.1016/j.jalz.2011.05.1402

Cited by 23 publications

(37 citation statements)

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“…Five days after the last injection, mice were tested for hippocampus-dependent spatial memory using a two-trial Y-maze task as described previously (Troquier et al, 2012). Briefly, the arms of the maze were 22 cm long, 6.4 cm wide, and 15 cm deep.…”

Section: Methodsmentioning

confidence: 99%

Neurotoxicity and Memory Deficits Induced by Soluble Low-Molecular-Weight Amyloid- 1-42 Oligomers Are Revealed In Vivo by Using a Novel Animal Model

Brouillette¹,

Caillierez²,

Zommer³

et al. 2012

Journal of Neuroscience

162

141

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Neuronal and synaptic degeneration are the best pathological correlates for memory decline in Alzheimer's disease (AD). Although the accumulation of soluble low-molecular-weight amyloid-␤ (A␤) oligomers has been suggested to trigger neurodegeneration in AD, animal models overexpressing or infused with A␤ lack neuronal loss at the onset of memory deficits. Using a novel in vivo approach, we found that repeated hippocampal injections of small soluble A␤ 1-42 oligomers in awake, freely moving mice were able to induce marked neuronal loss, tau hyperphosphorylation, and deficits in hippocampus-dependent memory. The neurotoxicity of small A␤ 1-42 species was observed in vivo as well as in vitro in association with increased caspase-3 activity and reduced levels of the NMDA receptor subunit NR2B. We found that the sequestering agent transthyretin is able to bind the toxic A␤ 1-42 species and attenuated the loss of neurons and memory deficits. Our novel mouse model provides evidence that small, soluble A␤ 1-42 oligomers are able to induce extensive neuronal loss in vivo and initiate a cascade of events that mimic the key neuropathological hallmarks of AD.

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Section: Methodsmentioning

confidence: 99%

Neurotoxicity and Memory Deficits Induced by Soluble Low-Molecular-Weight Amyloid- 1-42 Oligomers Are Revealed In Vivo by Using a Novel Animal Model

Brouillette¹,

Caillierez²,

Zommer³

et al. 2012

Journal of Neuroscience

162

141

View full text Add to dashboard Cite

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“…Importantly, as cognitive impairments closely correlate with the extension of tau pathology [132,133], removing neurofibrillary tangles has become one of the main therapeutic goals for the treatment of AD and FTD [134,135]. In this regard, it has been shown that both active and passive immunization against tau reduce its accumulation and slow or prevent behavioral deficits in transgenic mouse models of tauopathy [135][136][137][138][139][140][141][142].…”

Section: Immunotherapy Targeting Taumentioning

confidence: 99%

“…Active immunotherapy using phosphorylated tau epitopes has shown promising results in animal models [136,142], and 2 tau vaccines are currently in phase I trial for AD, AADvac-1, and ACI-35 (Table 1). AADvac-1 consists of a synthetic peptide derived from amino acids 294-305 of the tau sequence, although the precise molecular nature of the antigen has not been disclosed.…”

Section: Immunotherapy Targeting Taumentioning

confidence: 99%

“…Phosphorylation of tau at S422 has been linked to the relocalization of tau away from microtubules and toward the somatodendritic compartment of the neuron [149]. It has been shown that targeting the pS422 tau epitope with active vaccination decreases levels of insoluble phosphorylated tau and improves behavioral performance in transgenic mouse model of tauopathy [142]. Moreover, in a transgenic mouse model of AD, anti-tau pS422 antibodies are able to reduce accumulation of tau and induce its clearance via lysosomal pathways [88].…”

Section: Immunotherapy Targeting Taumentioning

confidence: 99%

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Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders

2016

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Disease-modifying alternatives are sorely needed for the treatment of neurodegenerative disorders, a group of diseases that afflict approximately 50 million Americans annually. Immunotherapy is one of the most developed approaches in this direction. Vaccination against amyloid-β, α-synuclein, or tau has been extensively explored, specially as the discovery that these proteins may propagate cell-to-cell and be accessible to antibodies when embedded into the plasma membrane or in the extracellular space. Likewise, the use of passive immunization approaches with specific antibodies against abnormal conformations of these proteins has also yielded promising results. The clinical development of immunotherapies for Alzheimer's disease, Parkinson's disease, frontotemporal dementia, dementia with Lewy bodies, and other neurodegenerative disorders is a field in constant evolution. Results to date suggest that immunotherapy is a promising therapeutic approach for neurodegenerative diseases that progress with the accumulation and prion-like propagation of toxic protein aggregates. Here we provide an overview of the most novel and relevant immunotherapeutic advances targeting amyloid-β in Alzheimer's disease, α-synuclein in Alzheimer's disease and Parkinson's disease, and tau in Alzheimer's disease and frontotemporal dementia.

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“…On the other hand, several studies on animal models have demonstrated that a reduction of tau pathology may produce an improvement in cognitive performance in the absence of obvious adverse effects [103][104][105][106][107]. Immunizing transgenic rats with recombinant misfolded truncated tau, before the occurrence of behavioral symptoms, reduces the level of both tau and p-tau and delays the onset of sensory-motor deficits without causing adverse effects [108].…”

Section: Bapineuzumabmentioning

confidence: 99%

Advances in the therapy of Alzheimer’s disease: targeting amyloid beta and tau and perspectives for the future

Hampel

Schneider

Giacobini

et al. 2014

Expert Review of Neurotherapeutics

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P2‐533: Targeting phospho‐Ser422 by active Tau immunotherapy in THY‐Tau22, a suitable therapeutic approach

Cited by 23 publications

References 0 publications

Neurotoxicity and Memory Deficits Induced by Soluble Low-Molecular-Weight Amyloid- 1-42 Oligomers Are Revealed In Vivo by Using a Novel Animal Model

Neurotoxicity and Memory Deficits Induced by Soluble Low-Molecular-Weight Amyloid- 1-42 Oligomers Are Revealed In Vivo by Using a Novel Animal Model

Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders

Advances in the therapy of Alzheimer’s disease: targeting amyloid beta and tau and perspectives for the future

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