LTP and memory impairment caused by extracellular A? and Tau oligomers is APP-dependent.

ABSTRACT: The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oA?) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oA? and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oA?, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oA? and oTau requires expression of APP. Finally, the toxic effect of both extracellular oA? and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oA?- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of A? and/or Tau.

SUBMITTER: Puzzo D 

PROVIDER: S-EPMC5529106 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature