1. Tau is not necessary for amyloid-β-induced synaptic and memory impairments
- Author
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Elentina K. Argyrousi, Erica Acquarone, Mauro Fa, Domenica Donatella Li Puma, Ottavio Arancio, Claudio Grassi, Hong Zhang, Elisa Calcagno, Daniela Puzzo, Luciano D'Adamio, Nicholas M. Kanaan, Elisa Zuccarello, Paul E. Fraser, and Agnieszka Staniszewski
- Subjects
0301 basic medicine ,Amyloid β ,Settore BIO/09 - FISIOLOGIA ,Tau protein ,Long-Term Potentiation ,tau Proteins ,Basal synaptic transmission ,Synaptic Transmission ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Memory ,Alzheimer Disease ,mental disorders ,Animals ,Mice, Knockout ,Amyloid beta-Peptides ,biology ,Mechanism (biology) ,Behavioral methods ,General Medicine ,Alzheimer's disease ,3. Good health ,Biochemistry of Alzheimer's disease ,Electrophysiology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Synaptic plasticity ,Synapses ,biology.protein ,Alzheimer’s disease ,Neuroscience ,Research Article - 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.
- Published
- 2020