Do astrocytes collaborate with neurons in spreading the "infectious" Aβ and Tau drivers of Alzheimer's disease?

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DOIResolve DOI: http://doi.org/10.1177/1073858414529828
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TypeArticle
Journal titleNeuroscientist
ISSN1073-8584
Volume21
Issue1
Pages929; # of pages: 21
Subjectamyloid beta protein; amyloid beta protein[1-42]; amyloid beta protein[25-35]; calcium antagonist; calcium sensing receptor; monomer; neuroprotective agent; nootropic agent; nps 2143; oligomer; tau protein; Alzheimer disease; astrocyte; brain cortex; cell interaction; cognition; default mode network; human; nerve cell; nerve cell degeneration; neuropathology; neuroprotection; protein function; protein phosphorylation; protein secretion; senile plaque
AbstractEvidence has begun emerging for the "contagious" and destructive Aβ42 (amyloid-beta42) oligomers and phosphorylated Tau oligomers as drivers of sporadic Alzheimer's disease (AD), which advances along a pathway starting from the brainstem or entorhinal cortex and leading to cognition-related upper cerebral cortex regions. Seemingly, Aβ42 oligomers trigger the events generating the neurotoxic Tau oligomers, which may even by themselves spread the characteristic AD neuropathology. It has been assumed that only neurons make and spread these toxic drivers, whereas their associated astrocytes are just janitorial bystanders/scavengers. But this view is likely to radically change since normal human astrocytes freshly isolated from adult cerebral cortex can be induced by exogenous Aβ25-35, an Aβ42 proxy, to make and secrete increased amounts of endogenous Aβ42. Thus, it would seem that the steady slow progression of AD neuropathology along specific cognition-relevant brain networks is driven by both Aβ42 and phosphorylated Tau oligomers that are variously released from increasing numbers of "contagion-stricken" members of tightly coupled neuron-astrocyte teams. Hence, we surmise that stopping the oversecretion and spread of the two kinds of "contagious" oligomers by such team members, perhaps via a specific CaSR (Ca2+-sensing receptor) antagonist like NPS 2143, might effectively treat AD.
Publication date
PublisherSAGE Publications
LanguageEnglish
AffiliationNational Research Council Canada; Human Health Therapeutics
Peer reviewedYes
NPARC number21275732
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Record identifierbc19e57a-a079-47b9-8031-8015922aea4e
Record created2015-07-14
Record modified2016-05-09
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