TY - JOUR
T1 - LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent
AU - Puzzo, Daniela
AU - Piacentini, Roberto
AU - Fá, Mauro
AU - Gulisano, Walter
AU - Li Puma, Domenica D.
AU - Staniszewski, Agnes
AU - Zhang, Hong
AU - Tropea, Maria Rosaria
AU - Cocco, Sara
AU - Palmeri, Agostino
AU - Fraser, Paul
AU - D’Adamio, Luciano
AU - Grassi, Claudio
AU - Arancio, Ottavio
N1 - Funding Information:
This work was supported by NIH grants R01AG049402 (OA), Italian FFO (DP and AP), Canadian Institute of Health Research TAD-117950 (PEF), Catholic University intramural funds (CG).
Publisher Copyright:
© Puzzo et al.
PY - 2017/7/11
Y1 - 2017/7/11
N2 - The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) 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 oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAβ and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAβ- 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 Ab and/or Tau.
AB - The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) 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 oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAβ and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAβ- 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 Ab and/or Tau.
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U2 - 10.7554/eLife.26991.001
DO - 10.7554/eLife.26991.001
M3 - Article
AN - SCOPUS:85026390814
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e26991
ER -
