Low glucose in brain may trigger Alzheimer’s disease: Study

WASHINGTON: Glucose deprivation in the brain may trigger the onset of cognitive decline, especially memory impairment - the earliest signs of Alzheimer’s disease, say scientists who have also found a protein that may be targeted to treat the disorder.

The hippocampus plays a key role in processing and storing memories. However, it relies exclusively on glucose for fuel without glucose, neurons starve and eventually die.

The new study is the first to directly link memory impairment to glucose deprivation in the brain specifically through a mechanism involving the accumulation of a protein known as phosphorylated tau.

“Phosphorylated tau precipitates and aggregates in the brain, forming tangles and inducing neuronal death,” said Domenico Pratico, Professor at Temple University in the US.

In general, a greater abun- dance of neurofibrillary tau tangles is associated with more severe dementia.

The study also is the first to identify a protein known as p38 as a potential alternate drug target in the treatment of Alzheimer’s disease.

Neurons activate p38 protein in response to glucose deprivation, possibly as a defensive mechanism. In the long run, however, its activation increases tau phosphorylation, making the problem worse.

To investigate the impact of glucose deprivation on the brain, Pratico’s team used a mouse model that recapitulates memory impairments and tau pathology in Alzheimer’s disease.

At about four or five months of age, some of the animals were treated with 2-deoxyglucose (DG), a compound that stops glucose from entering cells.