Tau is not necessary for amyloid-β-induced synaptic and memory impairments
Tau is not necessary for amyloid-β-induced synaptic and memory impairments
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DOI：
10.1172/jci137040
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发表时间：
2020-09-01
影响因子：
15.9
通讯作者：
Arancio, Ottavio
中科院分区：
文献类型：
--
作者：
Puzzo, Daniela;Argyrousi, Elentina K.;Arancio, Ottavio
The amyloid hypothesis posits that the amyloid-beta (A beta) 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 A beta 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 A beta-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 A beta and tau together are more suitable to combat AD than therapies against one or the other alone.
