Increased blood sugar levels may lead to Alzheimer’s disease by damaging a protein that is essential in fighting the disease’s early stages, a new study indicates.
The report, “Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer’s Disease,” appeared in the journal Scientific Reports.
Diabetes is a known risk factor for Alzheimer’s. Excessive levels of glucose and its breakdown products can damage proteins through a reaction called glycation, a process that has been associated with both Alzheimer’s and diabetes. However, scientists did not understand the specific molecular link between excess glucose and Alzheimer’s.
Researchers used brain samples from Alzheimer’s patients and healthy individuals to study glycation. They found that, in the early stages of Alzheimer’s, glycation damages a protein called macrophage migration inhibitory factor (MIF), which plays an important role in immune response, insulin regulation, oxidative stress and control of glucose levels — all of which have been implicated in Alzheimer’s.
After glycation, MIF can no longer stimulate glial cells, whose work is to prevent the accumulation of faulty proteins in the brain. As Alzheimer’s progresses, glycation of MIF increases, further contributing to neuronal damage.
Together, these findings suggest that MIF may be the molecular link between high glucose levels, diabetes and Alzheimer’s.
“We’ve shown that this enzyme is already modified by glucose in the brains of individuals at the early stages of Alzheimer’s disease,” Jean van den Elsen, the study’s co-senior author, said in a news release. “We are now investigating if we can detect similar changes in blood.“ Normally MIF would be part of the immune response to the buildup of abnormal proteins in the brain, and we think that because sugar damage reduces some MIF functions and completely inhibits others, that this could be a tipping point that allows Alzheimer’s to develop.”
Added Rob Williams, the study’s other senior author: “Knowing this will be vital to developing a chronology of how Alzheimer’s progresses, and we hope will help us identify those at risk of Alzheimer’s and lead to new treatments or ways to prevent the disease.”