Reduced brain sugar aggravates Alzheimer’s disease in mice

Disease progression in a mouse model of Alzheimer’s disease (AD) is worsened when glucose transport across the blood brain barrier is impaired, reports a paper published online in Nature Neuroscience this week.

Glucose in circulating blood provides the primary energy source to the brain. AD is characterised by early reductions in glucose transport, which has previously been associated with the glucose transporter, GLUT1; however, the influence of GLUT1 on the progression of the disease is not well understood.

Berislav Zlokovic and colleagues examined a mouse model of AD in which glucose transport is disrupted. By genetically manipulating GLUT1 in cells that make up the walls of blood vessels, the authors found that the reduction in GLUT1 worsened neurodegeneration, blood vessel breakdown and behavioral impairments in an AD mouse model. The study also shows that the alteration of energy metabolism and BBB breakdown precedes neurodegeneration and cognitive impairment in the AD mouse model. This study suggests that GLUT1 may be a potential therapeutic target to mitigate the cell death and vascular damages associated with AD and vascular dementia; however, more research is needed to determine the molecular mechanisms behind GLUT1 reduction.