Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

Alzheimer�s disease is defined by the presence of amyloid-β (Aβ) 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 Aβ 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 β-CTF, a protein precursor to Aβ peptides. In addition, the β-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 Aβ protein deposition. In addition, we found that circuit alterations may be caused by β-CTF, suggesting that early pharmacological prevention of brain circuit alterations might represent a more promising strategy towards delaying the development of Alzheimer�s disease.

Biography

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.