Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896097300> ?p ?o ?g. }
Showing items 1 to 92 of
92
with 100 items per page.
- W2896097300 abstract "Understanding the mechanisms that give rise to neurodegenerative diseases, in particular Alzheimer's disease, is of fundamental importance for the development of mechanism-based therapies. Alzheimer's disease is defined by the development of extracellular deposits of beta-amyloid and intraneuronal tau inclusions. Of these, tau inclusions correlate better with the loss of cognitive function. Moreover, tau inclusions are also found in a large number of other neurodegenerative diseases, including progressive supranuclear palsy, chronic traumatic encephalopathy and Pick's disease. Of the protein assemblies characteristic of human neurodegenerative diseases, those made of tau are the most common. Tau aggregates appear to spread through the brain via interconnected nerve cells, giving rise to the concept that they do so through prion-like mechanisms. In experimental systems, such as tauopathy mouse models, the spreading of tau pathology can be recapitulated following the injection of sonicated tau seeds. However, at present it is not possible to validate the prion-like spreading hypothesis from these experiments and extrapolate to the human brain. In order to address this fundamental question, we have quantified tau amplification at the molecular level by studying the evolution of single tau aggregates in vitro over extended times and fitted this data to obtain the rate constants for fibril elongation and fragmentation . We have then developed a simple model to estimate the rate of spreading through an animal or human brain based on these rate constants. We show that the spreading efficiency of tau aggregates depends on their elongation and fragmentation rates, as well as the availability of free cytosolic tau. Importantly, our spreading model is able to recapitulate spreading times in vivo and provides, for the first time, a quantitative framework for analysing the results from animal experiments and for linking them to the development of neuropathological changes in human brain. The prion-like propagation of tau occurs by elongation and fragmentation allowing a simple model to predict the spreading rate of tau assemblies in both animal models and humans. This model shows that inhibiting the rate of tau propagation would be an effective therapeutic strategy." @default.
- W2896097300 created "2018-10-26" @default.
- W2896097300 creator A5015741024 @default.
- W2896097300 creator A5037379608 @default.
- W2896097300 creator A5042822683 @default.
- W2896097300 creator A5050765603 @default.
- W2896097300 creator A5052514536 @default.
- W2896097300 creator A5065552925 @default.
- W2896097300 creator A5088531322 @default.
- W2896097300 creator A5091551842 @default.
- W2896097300 date "2018-07-01" @default.
- W2896097300 modified "2023-09-26" @default.
- W2896097300 title "O3‐01‐05: IN VITRO MEASUREMENTS OF TAU AGGREGATE ELONGATION AND FRAGMENTATION RATES ALLOW THE MODELLING OF PRION‐LIKE SPREADING IN HUMANS" @default.
- W2896097300 doi "https://doi.org/10.1016/j.jalz.2018.06.2774" @default.
- W2896097300 hasPublicationYear "2018" @default.
- W2896097300 type Work @default.
- W2896097300 sameAs 2896097300 @default.
- W2896097300 citedByCount "0" @default.
- W2896097300 crossrefType "journal-article" @default.
- W2896097300 hasAuthorship W2896097300A5015741024 @default.
- W2896097300 hasAuthorship W2896097300A5037379608 @default.
- W2896097300 hasAuthorship W2896097300A5042822683 @default.
- W2896097300 hasAuthorship W2896097300A5050765603 @default.
- W2896097300 hasAuthorship W2896097300A5052514536 @default.
- W2896097300 hasAuthorship W2896097300A5065552925 @default.
- W2896097300 hasAuthorship W2896097300A5088531322 @default.
- W2896097300 hasAuthorship W2896097300A5091551842 @default.
- W2896097300 hasConcept C12554922 @default.
- W2896097300 hasConcept C136238340 @default.
- W2896097300 hasConcept C142724271 @default.
- W2896097300 hasConcept C169760540 @default.
- W2896097300 hasConcept C185592680 @default.
- W2896097300 hasConcept C18903297 @default.
- W2896097300 hasConcept C190385971 @default.
- W2896097300 hasConcept C191015642 @default.
- W2896097300 hasConcept C202751555 @default.
- W2896097300 hasConcept C27523624 @default.
- W2896097300 hasConcept C2776925932 @default.
- W2896097300 hasConcept C2777739294 @default.
- W2896097300 hasConcept C2778426673 @default.
- W2896097300 hasConcept C2778670691 @default.
- W2896097300 hasConcept C2779134260 @default.
- W2896097300 hasConcept C2911139526 @default.
- W2896097300 hasConcept C3017944768 @default.
- W2896097300 hasConcept C502032728 @default.
- W2896097300 hasConcept C55493867 @default.
- W2896097300 hasConcept C71924100 @default.
- W2896097300 hasConcept C86803240 @default.
- W2896097300 hasConcept C95444343 @default.
- W2896097300 hasConcept C99454951 @default.
- W2896097300 hasConceptScore W2896097300C12554922 @default.
- W2896097300 hasConceptScore W2896097300C136238340 @default.
- W2896097300 hasConceptScore W2896097300C142724271 @default.
- W2896097300 hasConceptScore W2896097300C169760540 @default.
- W2896097300 hasConceptScore W2896097300C185592680 @default.
- W2896097300 hasConceptScore W2896097300C18903297 @default.
- W2896097300 hasConceptScore W2896097300C190385971 @default.
- W2896097300 hasConceptScore W2896097300C191015642 @default.
- W2896097300 hasConceptScore W2896097300C202751555 @default.
- W2896097300 hasConceptScore W2896097300C27523624 @default.
- W2896097300 hasConceptScore W2896097300C2776925932 @default.
- W2896097300 hasConceptScore W2896097300C2777739294 @default.
- W2896097300 hasConceptScore W2896097300C2778426673 @default.
- W2896097300 hasConceptScore W2896097300C2778670691 @default.
- W2896097300 hasConceptScore W2896097300C2779134260 @default.
- W2896097300 hasConceptScore W2896097300C2911139526 @default.
- W2896097300 hasConceptScore W2896097300C3017944768 @default.
- W2896097300 hasConceptScore W2896097300C502032728 @default.
- W2896097300 hasConceptScore W2896097300C55493867 @default.
- W2896097300 hasConceptScore W2896097300C71924100 @default.
- W2896097300 hasConceptScore W2896097300C86803240 @default.
- W2896097300 hasConceptScore W2896097300C95444343 @default.
- W2896097300 hasConceptScore W2896097300C99454951 @default.
- W2896097300 hasIssue "7S_Part_19" @default.
- W2896097300 hasLocation W28960973001 @default.
- W2896097300 hasOpenAccess W2896097300 @default.
- W2896097300 hasPrimaryLocation W28960973001 @default.
- W2896097300 hasRelatedWork W1590917599 @default.
- W2896097300 hasRelatedWork W2009033812 @default.
- W2896097300 hasRelatedWork W2142093242 @default.
- W2896097300 hasRelatedWork W2616038736 @default.
- W2896097300 hasRelatedWork W2618553145 @default.
- W2896097300 hasRelatedWork W2851646592 @default.
- W2896097300 hasRelatedWork W2896630904 @default.
- W2896097300 hasRelatedWork W2970734847 @default.
- W2896097300 hasRelatedWork W4294550854 @default.
- W2896097300 hasRelatedWork W4308970223 @default.
- W2896097300 hasVolume "14" @default.
- W2896097300 isParatext "false" @default.
- W2896097300 isRetracted "false" @default.
- W2896097300 magId "2896097300" @default.
- W2896097300 workType "article" @default.