Unified Model of Alzheimer’s Disease Pathobiology

Understanding of the pathobiology of Alzheimer’s disease (AD) has long been fragmented, with much research centered around biological mechanisms including amyloid β or tau proteins, inflammation, cell death pathways, glia, mitochondria and more. While these all deal with real facets in the biology of AD, they are limited in that they only address a portion of that biology. Many studies show a large number of changes in gene expression, attesting to the total biological complexity of AD.

 

Researchers at Arizona State University have developed a novel method for diagnosing the onset of Alzheimer’s Disease using a unified model of AD pathobiology. This model shows that cell stress results in the formation of stress granules which sequester components of the mechanism for nucleocytoplasmic exchange. This in turn affects epigenetic mechanisms, chromatin structure and subsequently massive changes in gene expression, which leads to defects and loss of synapses, altered protein processing and cellular metabolism and eventually cell death.

 

This model investigates stress granules and impaired nucleocytoplasmic transport, and integrates genetic and environmental risk factors into a unified framework that highlights early molecular dysfunction and suggests novel intervention points for AD and related neurodegenerative disorders.