Metabolism Measurements Predict Progress of Alzheimer’s disease

Metabolic studies could help cure Alzheimer’s disease (AD); measuring metabolism can predict the progress of the disease.

Before any symptoms of AD appear, metabolic processes start to change in the brain, according to an Israeli team from the Tel Aviv's Sackler School of Medicine (Tel Aviv, Israel) and TAU Blavatnik School of Computer Science (Tel Aviv, Israel). These scientists developed predictor models that use metabolic information to pinpoint the progression of Alzheimer's. These models were 90% accurate in predicting the stage of the disease.

To discover the connection between metabolism, brain functioning, and Alzheimer's disease, the researchers used data collected from the hippocampus region of the brain. Controlling memory and learning, this region of the brain is damaged as Alzheimer's progresses.

The team built a predictive model based on the number of metabolic genes found in the neurons and surrounding tissue, which relates abnormalities in these genes to the progression of the disease. Out of almost 1,500 genes, the researchers were able to select 50 genes that were the most predictive of Alzheimer's, said Dr. Shiri Stempler at the Tel Aviv University Sackler School of Medicine, noting that in Alzheimer's patients these genes either are over or under expressed.

Findings were compared from these 50 genes among Alzheimer's patients, healthy patients, and primates (including chimpanzees and rhesus monkeys) and discovered that in all except the Alzheimer's group, the number of specific genes was tightly limited, with little difference in their number between individuals among each of the species. This implied that these genes are significant to normal brain functioning, and their strict regulation in healthy patients is compromised by Alzheimer's disease.

Whether metabolic changes are a cause of the disease or merely a symptom remains a topic for future study. But the discovery of this connection is encouraging. "The correlation between metabolic gene expression and cognitive score in Alzheimer's patients is even higher than the correlation we see in medical literature between beta amyloid plaques–found in deposits in the brains of Alzheimer's patients–and cognitive score, pointing to a strong association between cognitive decline and an altered metabolism," Dr Stempler said.

Now the team will try to identify biomarkers in the blood that are associated with these metabolic changes. They may lead to detection and information about the disease's progression with an easy and noninvasive blood test. As their work advances, they hope to develop therapeutic strategies that are based around these alterations in the metabolic network to help Alzheimer's patients, such as medications that can reintroduce strict regulation over gene expression.

The research is the first step towards identifying biomarkers that may ensure better detection and analysis of the disease at an early stage, all with a simple blood test. It could also lead to novel therapies.

The study was reported in the journal Neurobiology of Aging.

Related Links:
Tel Aviv's Sackler School of Medicine
TAU Blavatnik School of Computer Science