Tau is not necessary for amyloid-β-induced synaptic and memory impairments

Daniela Puzzo, Elentina K. Argyrousi, Agnieszka Staniszewski, Hong Zhang, Elisa Calcagno, Elisa Zuccarello, Erica Acquarone, Mauro Fa', Domenica D. Li Puma, Claudio Grassi, Luciano D'Adamio, Nicholas M. Kanaan, Paul E. Fraser, Ottavio Arancio

Research output: Contribution to journalArticle

Abstract

The amyloid hypothesis posits that the amyloid-beta (Aβ) protein precedes and requires microtubule-associated protein tau in a sort of trigger-bullet mechanism leading to Alzheimer's disease (AD) pathology. This sequence of events has become dogmatic in the AD field and is used to explain clinical trial failures due to a late start of the intervention when Aβ already activated tau. Here, using a multidisciplinary approach combining molecular biological, biochemical, histopathological, electrophysiological, and behavioral methods, we demonstrated that tau suppression did not protect against Aβ-induced damage of long-term synaptic plasticity and memory, or from amyloid deposition. Tau suppression could even unravel a defect in basal synaptic transmission in a mouse model of amyloid deposition. Similarly, tau suppression did not protect against exogenous oligomeric tau-induced impairment of long-term synaptic plasticity and memory. The protective effect of tau suppression was, in turn, confined to short-term plasticity and memory. Taken together, our data suggest that therapies downstream of Aβ and tau together are more suitable to combat AD than therapies against one or the other alone.

Original languageEnglish
Pages (from-to)4831-4844
Number of pages14
JournalThe Journal of clinical investigation
Volume130
Issue number9
DOIs
Publication statusPublished - Sep 1 2020

Keywords

  • Alzheimer’s disease
  • Memory
  • Neuroscience

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Puzzo, D., Argyrousi, E. K., Staniszewski, A., Zhang, H., Calcagno, E., Zuccarello, E., Acquarone, E., Fa', M., Li Puma, D. D., Grassi, C., D'Adamio, L., Kanaan, N. M., Fraser, P. E., & Arancio, O. (2020). Tau is not necessary for amyloid-β-induced synaptic and memory impairments. The Journal of clinical investigation, 130(9), 4831-4844. https://doi.org/10.1172/JCI137040