Early Brain Network Alterations Are Correlated With ?-CTF In Alzheimer?s Transgenic Mouse Model | 21964
Journal of Alzheimers Disease & Parkinsonism
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Alzheimer?s disease is defined by the presence of amyloid-? (A?) and tau protein aggregates. However, increasing data
is suggesting that earlier phenomena such as brain network alterations rather that protein deposition could account
for the pathogenesis of the disease. Here we found that earlier fragments of A? processing rather than plaque deposits are
critically associated to abnormal function of brain networks. By measuring brain protein alterations in the hippocampus of
Alzheimer?s J20 transgenic mouse model at four weeks of age, we found significant increases in ?-CTF, a protein precursor
to A? peptides. In addition, the ?-CTF increase was found to be directly correlated with hippocampal circuit malfunction at
this age. By performing extracellular field recording method at the subiculum region in vitro, we found reduced theta-gamma
cross-frequency coupling at low (25-45 Hz) and high (150-250 Hz) gamma range. Interestingly, despite these network changes,
the J20 mice did not present cognitive deficit at this age. In summary, our data suggests that brain network alterations precede
the canonical A? protein deposition. In addition, we found that circuit alterations may be caused by ?-CTF, suggesting that
early pharmacological prevention of brain circuit alterations might represent a more promising strategy towards delaying the
development of Alzheimer?s disease.
Siddhartha Mondragon Rodriguez graduated in Chemical Engineering from Michoacan University of Saint Nicolas of Hidalgo (UMICH) in 1996 - 2002. Master
Degree (MsC) in Molecular Biomedicine from National School of Medicine from the National Polytechnic Institute of Mexico City. PhD from Center of Research
and Advanced Studies of the National Politechnical Institute in August 2005 - August 2009. PosdoctoralFellow from Universite de Montreal. Faculte de Medecine,
Departament de physiologie., Montreal, Qc, Canada. Posdoctoral Position in McGill University.
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