Dataset Information

Comprehensive phosphoproteome analysis unravels the core signaling network that initiates the earliest synapse pathology in preclinical Alzheimer's disease brain

ABSTRACT: Using a high-end mass spectrometry, we screened phosphoproteins and phosphopeptides in four types of Alzheimer's disease (AD) mouse models and human AD postmortem brains. We identified commonly changed phosphoproteins in multiple models and also determined phosphoproteins related to initiation of Abeta deposition in the mouse brain. We put the proteins on experimentally verified protein-protein interaction databases. Surprisingly most of the core phosphoproteins were directly connected, and they formed a functional network linked to synaptic spine formation. The change of the core network started at a preclinical stage even before histological Abeta deposition. Systems biology analyses suggested phosphorylation of MARCKS by over-activated kinases including PKCs and CaMKs initiates synapse pathology.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Hidenori Homma

LAB HEAD: Hitoshi Okazawa

PROVIDER: PXD001292 | Pride | 2014-09-10

REPOSITORIES: pride

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Comprehensive phosphoproteome analysis unravels the core signaling network that initiates the earliest synapse pathology in preclinical Alzheimer's disease brain.

Tagawa Kazuhiko K Homma Hidenori H Saito Ayumu A Fujita Kyota K Chen Xigui X Imoto Seiya S Oka Tsutomu T Ito Hikaru H Motoki Kazumi K Yoshida Chisato C Hatsuta Hiroyuki H Murayama Shigeo S Iwatsubo Takeshi T Miyano Satoru S Okazawa Hitoshi H

Human molecular genetics 20140917 2

Using a high-end mass spectrometry, we screened phosphoproteins and phosphopeptides in four types of Alzheimer's disease (AD) mouse models and human AD postmortem brains. We identified commonly changed phosphoproteins in multiple models and also determined phosphoproteins related to initiation of amyloid beta (Aβ) deposition in the mouse brain. After confirming these proteins were also changed in and human AD brains, we put the proteins on experimentally verified protein-protein interaction data ...[more]

PMID: 25231903

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	AD1M_1_F5.zip	Other