@article{01dc75b03e394f929a8cbf57f408b7fd,
title = "Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory",
abstract = "Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a 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 and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects 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 memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology.",
author = "M. F{\'a} and D. Puzzo and R. Piacentini and A. Staniszewski and H. Zhang and Baltrons, {M. A.} and {Li Puma}, {D. D.} and I. Chatterjee and J. Li and F. Saeed and Berman, {H. L.} and C. Ripoli and W. Gulisano and J. Gonzalez and H. Tian and Costa, {J. A.} and P. Lopez and E. Davidowitz and Yu, {W. H.} and V. Haroutunian and Brown, {L. M.} and A. Palmeri and Sigurdsson, {E. M.} and Duff, {K. E.} and Teich, {A. F.} and Honig, {L. S.} and M. Sierks and Moe, {J. G.} and L. D'Adamio and C. Grassi and Kanaan, {N. M.} and Fraser, {P. E.} and O. Arancio",
note = "Funding Information: This work was supported by NIH grants NS049442 and AG049402 (OA), P50AG008702 (LSH), R01AG017761 (DPD), R43AG029777, R44AG029777, R44AG029777B and R44AG033474 (JGM), AG02219 (VH), R01NS082730 (NMK), AG041531, AG033007 and AG048971 (LD) (http://www.nih.gov). This work was also supported by BrightFocus Foundation A2013364S (NMK) (http://www.brightfocus.org), Universit{\`a} Cattolica Intramural Funds Linea D3.2-2103 (CG) (http://www.unicatt.it), Alzheimer{\textquoteright}s Association IIRG-11-205343 (MF), IIRG-09-134220 (DP), and ZEN-11-201425 (LD) (http://www.alz.org), Ministry of Science and Education, Spain PR2010-0297 (MAB) (http://www.mecd.gob.es), Canadian Institutes of Health Research MOP-115056 (PEF) (http://www. alzheimer.ca/en/on), ADDF 271209 (JGM and OA) (http://alzdiscovery.org). Brain specimens were provided by JP Vonsattel and EP Cortes of the NY Brain Bank of Columbia and Mt Sinai School of Medicine, NY. We also thank N. Hansmeier for assistance with AFM, Drs F. Mancia, L. Shapiro, S. Mannepalli, and G. Sciara for assistance with chromatography, Dr. Rong Cheng and Joseph Lee for assistance with statistical analysis of the AFM data, V. Kansara for help with cultures, L. Mammana and M.R. Tropea for help with behavioral studies.",
year = "2016",
month = jan,
day = "20",
doi = "10.1038/srep19393",
language = "English (US)",
volume = "6",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}