Skip global navigation and read the article

Skip global navigation and go to local navigation

Skip global navigation and go to footer navigation



Home  > Department of Neuropathology  > Research Activities  > Molecular basis for the earlist synapse pathology in preclinical Alzheimer's disease brain (2014)

Molecular basis for the earlist synapse pathology in preclinical Alzheimer's disease brain (2014)


We elucidated molecular basis for the earliest synapse pathology in preclinical Alzheimer's disease (AD) brain. In this study, we performed comprehensive phosphoprotein analysis with brain samples from AD patients and four mouse models by using high-end mass spectrometry, and analyzed the data by methods of systems biology using a super computer. We found that 17 phosphoproteins related to synapse functions are changed in the brains of mouse AD models and human AD patients.


Especially, the change of MARCKS started at a a preclinical stage even before histological Aβ deposition. Two-photon microscopic observation revealed recovery of abnormal spine formation in the AD model mice by targeting MARCKS or by inhibiting its candidate kinases.
This study proposed a novel strategy of AD treatment which targets the earliest pathology.