High blood sugar makes Alzheimer’s plaque more toxic to the brain

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The study supports growing evidence pointing to glucose levels and vascular damage as contributors to the progression of the deadly form of dementia.

High blood-sugar levels, such as those linked with Type 2 diabetes, make beta amyloid protein associated with Alzheimer’s disease dramatically more toxic to cells lining blood vessels in the brain, according to a new study published in the Journal of Alzheimer’s Disease.


“Previously, it was believed that Alzheimer’s disease was due to the accumulation of ‘tangles’ in neurons in the brain from overproduction and reduced removal of beta amyloid protein,” said senior investigator David Busija, Regents professor and chair of Pharmacology at Tulane University School of Medicine, New Orleans, USA. “While neuronal involvement is a major factor in Alzheimer’s development, recent evidence indicates damaged cerebral blood vessels compromised by high blood sugar play a role. Even though the links among Type 2 diabetes, brain blood vessels and Alzheimer’s progression are unclear, hyperglycaemia appears to play a role.”

Researchers studied cell cultures taken from the lining of cerebral blood vessels, one from normal rats and another from mice with uncontrolled chronic diabetes. They exposed the cells to beta amyloid and different levels of glucose and later measured their viability. Cells exposed to high glucose or beta amyloid alone showed no changes in viability. However, when exposed to hyperglycaemic conditions and beta amyloid, viability decreased by 40%. Researchers suspect that the damage is due to oxidative stress from the mitochondria of the cell.


The cells from diabetic mice were more susceptible to damage and death to beta amyloid protein, even at normal glucose levels. The increased toxicity of beta amyloid may damage the blood-brain barrier, disrupt normal blood flow to the brain and decrease clearance of beta amyloid protein.

The study’s findings underscore the need to aggressively control blood sugar levels in diabetic individuals, Busija said.

 

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