University of Zurich

About: University of Zurich is a education organization based out in Zurich, Switzerland. It is known for research contribution in the topics: Population & Medicine. The organization has 50842 authors who have published 124042 publications receiving 5304521 citations. The organization is also known as: UZH & Uni Zurich.

Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice

Abstract: Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta)-containing plaques, neurofibrillary tangles, and neuron and synapse loss. Tangle formation has been reproduced in P301L tau transgenic pR5 mice, whereas APP(sw)PS2(N141I) double-transgenic APP152 mice develop Abeta plaques. Cross-breeding generates triple transgenic ((triple)AD) mice that combine both pathologies in one model. To determine functional consequences of the combined Abeta and tau pathologies, we performed a proteomic analysis followed by functional validation. Specifically, we obtained vesicular preparations from (triple)AD mice, the parental strains, and nontransgenic mice, followed by the quantitative mass-tag labeling proteomic technique iTRAQ and mass spectrometry. Within 1,275 quantified proteins, we found a massive deregulation of 24 proteins, of which one-third were mitochondrial proteins mainly related to complexes I and IV of the oxidative phosphorylation system (OXPHOS). Notably, deregulation of complex I was tau dependent, whereas deregulation of complex IV was Abeta dependent, both at the protein and activity levels. Synergistic effects of Abeta and tau were evident in 8-month-old (triple)AD mice as only they showed a reduction of the mitochondrial membrane potential at this early age. At the age of 12 months, the strongest defects on OXPHOS, synthesis of ATP, and reactive oxygen species were exhibited in the (triple)AD mice, again emphasizing synergistic, age-associated effects of Abeta and tau in perishing mitochondria. Our study establishes a molecular link between Abeta and tau protein in AD pathology in vivo, illustrating the potential of quantitative proteomics.

Consensus statement on concussion in sport: The 4th international conference on concussion in sport, Zurich, November 2012

Abstract: Paul McCrory, MBBS, PhD*; Willem H. Meeuwisse, MD, PhD†; Mark Aubry, MD‡; Robert C. Cantu, MD§; Jiři Dvořak, MD||; Ruben J. Echemendia, PhD¶; Lars Engebretsen, MD, PhD#; Karen Johnston, MD, PhD**; Jeffrey S. Kutcher, MD††; Martin Raftery, MBBS‡‡; Allen Sills, MD§§; Brian W. Benson, MD, PhD||||; Gavin A. Davis, MBBS¶¶; Richard Ellenbogen, MD##; Kevin M. Guskiewicz, PhD***; Stanley A. Herring, MD†††; Grant L. Iverson, PhD‡‡‡; Barry D. Jordan, MD§§§; James Kissick, MD||||||; Michael McCrea, PhD¶¶¶; Andrew S. McIntosh, PhD###; David Maddocks, LLB, PhD****; Michael Makdissi, MBBS, PhD††††; Laura Purcell, MD‡‡‡‡; Margot Putukian, MD§§§§; Kathryn Schneider, PhD||||||||; Charles H. Tator, MD, PhD¶¶¶¶; Michael Turner, MD####

Options and considerations when selecting a quantitative proteomics strategy

Abstract: The vast majority of proteomic studies to date have relied on mass spectrometric techniques to identify, and in some cases quantify, peptides that have been generated by proteolysis. Current approaches differ in the types of instrument used, their performance profiles, the manner in which they interface with biological research strategies, and their reliance on and use of prior information. Here, we consider the three main mass spectrometry (MS)-based proteomic approaches used today: shotgun (or discovery), directed and targeted strategies. We discuss the principles of each technique, their strengths and weaknesses and the dependence of their performance profiles on the composition of the biological sample. Our goal is to provide a rational framework for selecting strategies optimally suited to address the specific research issue under consideration.