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 multidisplinary 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, as well as 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

Puzzo, D., Argyrousi, E., Staniszewski, A., Zhang, H., Calcagno, E., Zuccarello, E., Acquarone, E., Fà, M., Li Puma, D. D., Grassi, C., D'adamio, L., Kanaan, N., Fraser, P., Arancio, O., Tau is not necessary for amyloid-beta-induced synaptic and memory impairments, <<THE JOURNAL OF CLINICAL INVESTIGATION>>, 2020; 2020 (9/130): 4831-4844. [doi:10.1172/JCI137040] [http://hdl.handle.net/10807/160991]

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

Li Puma DD;Grassi C;
2020

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 multidisplinary 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, as well as 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
eng
Puzzo, D., Argyrousi, E., Staniszewski, A., Zhang, H., Calcagno, E., Zuccarello, E., Acquarone, E., Fà, M., Li Puma, D. D., Grassi, C., D'adamio, L., Kanaan, N., Fraser, P., Arancio, O., Tau is not necessary for amyloid-beta-induced synaptic and memory impairments, <>, 2020; 2020 (9/130): 4831-4844. [doi:10.1172/JCI137040] [http://hdl.handle.net/10807/160991]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/160991
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