Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to playa major role in Alzheimer’s disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex andneocortices independently of Aβ, eventually leading to memory loss. Here we show that a briefexposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces animpairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβlevels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. Theseeffects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memoryimpairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offeringnew therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associatedwith Aβ and tau pathology.
|Titolo:||Extracellular Tau oligomers produce an immediate impairment of LTP and memory.|
|Data di pubblicazione:||2016|
|Citazione:||Extracellular Tau oligomers produce an immediate impairment of LTP and memory. / Fa, M; Puzzo, Daniela; Piacentini, R; Staniszewski, A; Zhang, H; Baltrons, Ma; Li Puma, Dd; Chatterjee, I; Li, J; Saeed, F; Berman, Hl; Ripoli, C; Gulisano, W; Gonzalez, J; Tian, H; Costa, Ja; Lopez, P; Davidowitz, E; Yu, Wh; Haroutunian, V; Brown, Lm; Palmeri, Agostino; Sigurdsson, Em; Duff, Ke; Teich, Af; Honig, Ls; Sierks, M; Moe, Jg; D’Adamio, L; Grassi, C; Kanaan, Nm; Fraser, Pe; Arancio, O.. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 5(2016), pp. 19393-19408.|
|Appare nelle tipologie:||1.1 Articolo in rivista|