Tubulin Isotypes and Posttranslational Modifications in Vascular Dementia and Alzheimer's Disease.

Abstract

Vascular dementia (VaD) and Alzheimer's disease (AD) are the two most common forms of dementia. Although these two types of dementia have different etiologies, they share some similarities in their pathophysiology, such as neuronal loss and decreased levels of tau protein. We hypothesize that these can have an impact upon the molecular changes in tubulin, precede the neuronal cell loss, and lead to changes in cytoskeletal associated proteins, as documented in both VaD and AD. We characterized different isotypes of tubulin together with their posttranslational modifications, as well as several microtubule associated proteins (MAPs), such as tau protein, MAP2 and MAP6, all together known as the tubulin code. We performed western blotting in human brain homogenates of controls and AD and VaD subjects. We report that the levels of different tubulin isotypes differ depending on the dementia type and the brain area being studied: whereas α-tubulin is increased in the temporal lobe of VaD patients, it is decreased in the frontal lobe of AD patients. In VaD patients, the frontal lobe had a decrease in tyrosinated tubulin, which was accompanied by a decrease in tau protein and a tendency for lower levels of MAP2. Our findings highlight distinct changes in the tubulin code in VaD and AD, suggesting a therapeutic opportunity for different dementia subtypes in the future.