title: Do astrocytes collaborate with neurons in spreading the "infectious" aβ and Tau drivers of Alzheimer's disease?
abstract: Evidence 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 (Ca(2+)-sensing receptor) antagonist like NPS 2143, might effectively treat AD.
authors.affiliation: Department of Life & Reproduction Sciences, The University of Verona Medical School, Verona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dal Prà
authors.affiliation: Department of Life & Reproduction Sciences, The University of Verona Medical School, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Chiarini
authors.affiliation: Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gui
authors.affiliation: National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Balu
authors.initials: B
authors.lastname: Chakravarthy
authors.affiliation: Department of Life & Reproduction Sciences, The University of Verona Medical School, Verona, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pacchiana
authors.affiliation: Department of Life & Reproduction Sciences, The University of Verona Medical School, Verona, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gardenal
authors.affiliation: National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: James F
authors.initials: JF
authors.lastname: Whitfield
authors.affiliation: Department of Life & Reproduction Sciences, The University of Verona Medical School, Verona, Italy uarmato@gmail.com.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins
keywords: Alzheimer’s disease; amyloid-beta; astrocyte–neuron collaboration; calcilytics; calcium-sensing receptor; oligomers; tau