MAR 15, 2017

Glucose and Alzheimer's: Is There a Connection?

WRITTEN BY: Brenda Kelley Kim
Alzheimer’s disease (AD) is well known for its devastating effect on memory and cognition. People who deal with it slowly lose the ability to remember how to perform routine daily tasks. They also slowly lose touch with reality, often not remembering loved ones and family members. The goal of a good amount of research is to understand and recognize early signs of the disease. That is no easy task however. One of the indicators of AD is a decline in glucose levels in the brain. It begins in the early stages of the disease, when there are just small signs on cognitive impairment. This is the problem in AD, the early signs are often chalked up to simple age-related forgetfulness.
It’s not fully clear yet from research whether the decline in brain glucose is a result of AD or a precursor. It’s even been considered as a possible cause but there is no definite research that can determine that yet. A team from the Lewis Katz School of Medicine at Temple University might be on the right track however. A study recently completed by scientists there now shows definite evidence that glucose deprivation in the brain triggers the onset of cognitive decline. It’s especially evident in memory issues.
 
Domenico Praticò, MD, Professor in the Center for Translational Medicine at the Lewis Katz School of Medicine at Temple University (LKSOM) stated in a press release, "In recent years, advances in imaging techniques, especially positron emission tomography (PET), have allowed researchers to look for subtle changes in the brains of patients with different degrees of cognitive impairment. One of the changes that has been consistently reported is a decrease in glucose availability in the hippocampus." It’s been well-established that the hippocampus is the key part of the brain that is active in making and storing memories. And the brain relies on glucose as fuel, so a decline in the levels of glucose in key brain areas is significant in the onset of Alzheimer’s.
 
The study from the team at LKSOM was published online January 31 in the journal Translational Psychiatry. It’s the first study of it’s kind to link memory impairment to glucose deprivation. The mechanism behind this link involves the accumulation of a protein known as phosphorylated tau. Dr. Praticò explained, “Phosphorylated tau precipitates and aggregates in the brain, forming tangles and inducing neuronal death," explained. In general, a greater abundance of neurofibrillary tau tangles is associated with more severe dementia.”
 
The research is also significant because it identifies the protein known as p38 as being a promising drug target for researchers looking at medications to treat Alzheimer’s. Initially neurons activate this protein when glucose in the brain dips, but eventually, the activation of p38 causes the disease to progress quicker because it increases the rate of tau phosphorylation
 
Dr. Praticò's team used a mouse model to investigate memory impairments and glucose levels in the brain. By injecting mice with 2-deoxyglucose (DG) which stops glucose from entering the brain, and the measuring cognitive impairment, it was shown that the glucose deficient mice performed significantly worse than the untreated mice who had normal glucose production. Looking at the brains of the glucose deprived mice further confirmed the hypothesis when researchers saw abnormal synaptic function as well as high levels of cell death an increased amounts of phosphorylated tau. Even in small increments, as happens in diabetes patients, there was a demonstrable effect on cognition, linking the disease of diabetes and it’s accompanying insulin resistance to the progression of Alzheimer’s.
 
The team hopes to continue further work where the protein p38 is inhibited to see if memory impairments can be reversed. Any possible drug targets that come about from this research cold be an “exciting avenue” according to Praticò. The following video explains how the brain uses glucose. While it deals with too much glucose, the lack of glucose is emerging as a concern as well, check it out.

Sources: MSN Translational Psychiatry Temple University