New clues to Alzheimer's treatment found

Japanese researchers have discovered a possible pathological mechanism of Alzheimer's, which could pave the way for an effective therapy for the currently incurable disease.
Researchers led by Kazuhiko Tagawa from Tokyo Medical and Dental University used comprehensive phosphoproteome analysis to unravel the core signalling network that initiates the earliest synapse pathology in preclinical Alzheimer's disease (AD) brain.
Using a high-end mass spectrometry, researchers screened phosphoproteins and phosphopeptides in four types of AD mouse models and human AD postmortem brains, Xinhua news agency quoted the website news.Mynavi.Jp as saying.
"We identified commonly changed phosphoproteins in multiple models and also determined phosphoproteins related to initiation of A deposition in the mouse brain," they said.

Researchers put these proteins on experimentally verified protein-protein interaction databases, after confirming the proteins were also changed in human AD brains.
"Surprisingly most of the core phosphoproteins were directly connected, and they formed a functional network linked to synaptic spine formation," researchers said.

Researchers found the change of the core network started at a preclinical stage even before histological A deposition.
Systems biology analyses suggested phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS) by over-activated kinases including PKCs and CaMKs initiates synapse pathology, the report said.
The study was published in the journal Human Molecular Genetics.