PMID- 32952546
OWN - NLM
STAT- MEDLINE
DCOM- 20210803
LR  - 20240329
IS  - 1687-5443 (Electronic)
IS  - 2090-5904 (Print)
IS  - 1687-5443 (Linking)
VI  - 2020
DP  - 2020
TI  - Circuitry and Synaptic Dysfunction in Alzheimer's Disease: A New Tau Hypothesis.
PG  - 2960343
LID - 10.1155/2020/2960343 [doi]
LID - 2960343
AB  - For more than five decades, the field of Alzheimer's disease (AD) has focused on 
      two main hypotheses positing amyloid-beta (Abeta) 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.
CI  - Copyright (c) 2020 Siddhartha Mondragon-Rodriguez et al.
FAU - Mondragon-Rodriguez, Siddhartha
AU  - Mondragon-Rodriguez S
AUID- ORCID: 0000-0003-1335-226X
AD  - CONACYT National Council for Science and Technology, Mexico, Mexico.
AD  - UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, 
      National Autonomous University of Mexico, Queretaro, Mexico.
FAU - Salgado-Burgos, Humberto
AU  - Salgado-Burgos H
AD  - UADY Neurosciences Department, Autonomous University of Yucatan, 97000 Merida, 
      Yucatan, Mexico.
FAU - Pena-Ortega, Fernando
AU  - Pena-Ortega F
AD  - UNAM Developmental Neurobiology and Neurophysiology, Institute of Neurobiology, 
      National Autonomous University of Mexico, Queretaro, Mexico.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200901
PL  - United States
TA  - Neural Plast
JT  - Neural plasticity
JID - 100883417
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Brain/*metabolism
MH  - Humans
MH  - Microtubules/metabolism
MH  - Models, Neurological
MH  - Neuronal Plasticity
MH  - Neurons/*metabolism
MH  - Phosphorylation
MH  - Synapses/*metabolism
MH  - tau Proteins/*metabolism
PMC - PMC7481966
COIS- The authors declare no competing financial interests.
EDAT- 2020/09/22 06:00
MHDA- 2021/08/04 06:00
PMCR- 2020/09/01
CRDT- 2020/09/21 06:06
PHST- 2020/03/13 00:00 [received]
PHST- 2020/07/20 00:00 [revised]
PHST- 2020/08/06 00:00 [accepted]
PHST- 2020/09/21 06:06 [entrez]
PHST- 2020/09/22 06:00 [pubmed]
PHST- 2021/08/04 06:00 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
AID - 10.1155/2020/2960343 [doi]
PST - epublish
SO  - Neural Plast. 2020 Sep 1;2020:2960343. doi: 10.1155/2020/2960343. eCollection 
      2020.