Systems biology of Alzheimer's disease: How diverse molecular changes result in memory impairment in AD

Alzheimer's disease (AD) is a protein misfolding-based rapid cognitive impairment in the aging brain. Because of its very widespread molecular background, AD has been approached using genomic and proteomic methods and has accumulated a large body of data during the last 15 years. In this review, we summarize the systems biology data on AD and pay particular attention to the proteomic changes in AD. Applying a systems biology model of the synapse, we attempt to integrate protein changes and provide an explanation of why seemingly diverse molecular changes result in memory impairment. We also summarize the present state of cerebrospinal fluid (CSF) and blood biomarker studies for the diagnosis of AD as well as the results of proteomic studies in tissue cultures and animal models. Finally, we give a systems biology model of AD explaining how AD can develop in an individual manner in each particular subject but always results in a rapidly developing dementia and memory impairment.

Research highlights► β-Amyloid overproduction and accumulation. ► Reduced energy metabolism and overproduction of reactive oxygen species due to mitochondrial dysfunction. ► Abnormal protein folding and phosphorylation. ► Impairment of synaptic communication. ► Memory impairment. ► Neuronal loss.