LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent

Daniela Puzzo, Roberto Piacentini, Mauro Fá, Walter Gulisano, Domenica D. Li Puma, Agnes Staniszewski, Hong Zhang, Maria Rosaria Tropea, Sara Cocco, Agostino Palmeri, Paul Fraser, Luciano D’Adamio, Claudio Grassi, Ottavio Arancio

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere26991
JournaleLife
Volume6
DOIs
StatePublished - Jul 11 2017

Fingerprint

Long-Term Memory
Long-Term Potentiation
Amyloid beta-Protein Precursor
Oligomers
Data storage equipment
Neurodegenerative diseases
tau Proteins
Poisons
Amyloid beta-Peptides
Amyloid
Neurodegenerative Diseases
Alzheimer Disease
Defects

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Puzzo, D., Piacentini, R., Fá, M., Gulisano, W., Li Puma, D. D., Staniszewski, A., ... Arancio, O. (2017). LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent. eLife, 6, [e26991]. https://doi.org/10.7554/eLife.26991.001

LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent. / Puzzo, Daniela; Piacentini, Roberto; Fá, Mauro; Gulisano, Walter; Li Puma, Domenica D.; Staniszewski, Agnes; Zhang, Hong; Tropea, Maria Rosaria; Cocco, Sara; Palmeri, Agostino; Fraser, Paul; D’Adamio, Luciano; Grassi, Claudio; Arancio, Ottavio.

In: eLife, Vol. 6, e26991, 11.07.2017.

Research output: Contribution to journalArticle

Puzzo, D, Piacentini, R, Fá, M, Gulisano, W, Li Puma, DD, Staniszewski, A, Zhang, H, Tropea, MR, Cocco, S, Palmeri, A, Fraser, P, D’Adamio, L, Grassi, C & Arancio, O 2017, 'LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent', eLife, vol. 6, e26991. https://doi.org/10.7554/eLife.26991.001
Puzzo D, Piacentini R, Fá M, Gulisano W, Li Puma DD, Staniszewski A et al. LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent. eLife. 2017 Jul 11;6. e26991. https://doi.org/10.7554/eLife.26991.001
Puzzo, Daniela ; Piacentini, Roberto ; Fá, Mauro ; Gulisano, Walter ; Li Puma, Domenica D. ; Staniszewski, Agnes ; Zhang, Hong ; Tropea, Maria Rosaria ; Cocco, Sara ; Palmeri, Agostino ; Fraser, Paul ; D’Adamio, Luciano ; Grassi, Claudio ; Arancio, Ottavio. / LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent. In: eLife. 2017 ; Vol. 6.
@article{61535495087f4f92a46b80ac82115aaa,
title = "LTP and memory impairment caused by extracellular Aβ and tau oligomers is APP- dependent",
abstract = "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.",
author = "Daniela Puzzo and Roberto Piacentini and Mauro F{\'a} and Walter Gulisano and {Li Puma}, {Domenica D.} and Agnes Staniszewski and Hong Zhang and Tropea, {Maria Rosaria} and Sara Cocco and Agostino Palmeri and Paul Fraser and Luciano D’Adamio and Claudio Grassi and Ottavio Arancio",
year = "2017",
month = "7",
day = "11",
doi = "10.7554/eLife.26991.001",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=85026390814&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026390814&partnerID=8YFLogxK

U2 - 10.7554/eLife.26991.001

DO - 10.7554/eLife.26991.001

M3 - Article

VL - 6

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e26991

ER -