Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis
For more than five decades, the field of Alzheimer’s disease (AD) has focused on two main hypotheses positing amyloid-beta (Aβ) and Tau phosphorylation (pTau) as key pathogenic mediators. In line with these canonical hypotheses, several groups around the world have shown that the synaptotoxicity in...
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| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/2960343 |
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| author | Siddhartha Mondragón-Rodríguez Humberto Salgado-Burgos Fernando Peña-Ortega |
| author_facet | Siddhartha Mondragón-Rodríguez Humberto Salgado-Burgos Fernando Peña-Ortega |
| author_sort | Siddhartha Mondragón-Rodríguez |
| collection | DOAJ |
| description | For more than five decades, the field of Alzheimer’s disease (AD) has focused on two main hypotheses positing amyloid-beta (Aβ) and Tau phosphorylation (pTau) as key pathogenic mediators. In line with these canonical hypotheses, several groups around the world have shown that the synaptotoxicity in AD depends mainly on the increase in pTau levels. Confronting this leading hypothesis, a few years ago, we reported that the increase in phosphorylation levels of dendritic Tau, at its microtubule domain (MD), acts as a neuroprotective mechanism that prevents N-methyl-D-aspartate receptor (NMDAr) overexcitation, which allowed us to propose that Tau protein phosphorylated near MD sites is involved in neuroprotection, rather than in neurodegeneration. Further supporting this alternative role of pTau, we have recently shown that early increases in pTau close to MD sites prevent hippocampal circuit overexcitation in a transgenic AD mouse model. Here, we will synthesize this new evidence that confronts the leading Tau-based AD hypothesis and discuss the role of pTau modulating neural circuits and network connectivity. Additionally, we will briefly address the role of brain circuit alterations as a potential biomarker for detecting the prodromal AD stage. |
| format | Article |
| id | doaj-art-c13d3de12b2f4d0eba99a421552b9ca3 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-c13d3de12b2f4d0eba99a421552b9ca32025-02-03T00:58:44ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/29603432960343Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau HypothesisSiddhartha Mondragón-Rodríguez0Humberto Salgado-Burgos1Fernando Peña-Ortega2CONACYT National Council for Science and Technology, México, MexicoUADY Neurosciences Department, Autonomous University of Yucatán, 97000 Mérida, Yucatán, MexicoUNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, National Autonomous University of México, Querétaro, MexicoFor more than five decades, the field of Alzheimer’s disease (AD) has focused on two main hypotheses positing amyloid-beta (Aβ) and Tau phosphorylation (pTau) as key pathogenic mediators. In line with these canonical hypotheses, several groups around the world have shown that the synaptotoxicity in AD depends mainly on the increase in pTau levels. Confronting this leading hypothesis, a few years ago, we reported that the increase in phosphorylation levels of dendritic Tau, at its microtubule domain (MD), acts as a neuroprotective mechanism that prevents N-methyl-D-aspartate receptor (NMDAr) overexcitation, which allowed us to propose that Tau protein phosphorylated near MD sites is involved in neuroprotection, rather than in neurodegeneration. Further supporting this alternative role of pTau, we have recently shown that early increases in pTau close to MD sites prevent hippocampal circuit overexcitation in a transgenic AD mouse model. Here, we will synthesize this new evidence that confronts the leading Tau-based AD hypothesis and discuss the role of pTau modulating neural circuits and network connectivity. Additionally, we will briefly address the role of brain circuit alterations as a potential biomarker for detecting the prodromal AD stage.http://dx.doi.org/10.1155/2020/2960343 |
| spellingShingle | Siddhartha Mondragón-Rodríguez Humberto Salgado-Burgos Fernando Peña-Ortega Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis Neural Plasticity |
| title | Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis |
| title_full | Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis |
| title_fullStr | Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis |
| title_full_unstemmed | Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis |
| title_short | Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis |
| title_sort | circuitry and synaptic dysfunction in alzheimer s disease a new tau hypothesis |
| url | http://dx.doi.org/10.1155/2020/2960343 |
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