Exogenous β-amyloid peptide interferes with GLUT4 localization in neurons

• Internalized Aβ42 affects GLUT4 distribution and reduces GLUT4 at the cell surface.
• There is an increase in the colocalization between myosin Vb and GLUT4.
• Higher Aβ40 peptide concentration inhibited the internalization of the Aβ42 peptide.

Aging represents a major risk factor for numerous illnesses that are of increasing importance to society, including two of the most prevalent: diabetes and Alzheimer׳s disease. Studies have shown that diabetes is a risk factor for spontaneous Alzheimer׳s disease. While these studies suggest that diabetes can contribute to Alzheimer׳s disease, the implications of AD on diabetes are practically unexplored. The major mediator of the pathophysiological effects, the Aβ42 peptide, has been shown to enter neurons and lead to an alteration of the intracellular distribution of the molecular motor myosin Vb. Myosin Vb functions in memory and learning by participating in the strengthening of the long-term potentiation (LTP) of synaptic transmissions. It has also been implicated in the translocation of the glucose transporter, GLUT4, to the plasma membrane in response to insulin, a process that is defective in diabetes. Here, the effect on GLUT4 upon entry of the Aβ42 peptide into cultured chick retinal neurons was explored. The results suggest an alteration in distribution and a reduced level at the cell surface, as well as an increased colocalization with myosin Vb, which can partially explain the changes in glucose metabolism associated with AD. It is also shown that the presence of the Aβ40 peptide inhibits the internalization of the Aβ42 peptide in cultured cells. Together, the results provide additional targets for the development of therapeutics against the progression and effects of Alzheimer׳s disease.