Early clues regarding the progression of Alzheimer’s disease can be found by measuring the brain’s metabolism, according to new research.
In the very early stages of the disease, before any symptoms appear, metabolic processes are already beginning to change in the brain, said Ph.D. candidate Shirr Templar of Tel Aviv University’s Sacker Faculty of Medicine.
Working with Professors Eytan Rupee and Loire Wolf of the university’s Blavatnik School of Computer Science, Stempler developed predictor models that use metabolic information to pinpoint the progression of Alzheimer’s. She reported that these models were 90 percent accurate in predicting the stage of the disease.
“We hope that by studying metabolism, and the alterations to metabolism that occur in the very early stages of the disease, we can find new therapeutic strategies,” she said.
To delve deeper into the connection between metabolism, brain functioning, and Alzheimer’s disease, the researchers used data collected from the hippocampus region of the brain, which controls memory and learning and is damaged as Alzheimer’s progresses.
Based on the number of metabolic genes found in the neurons and surrounding tissue, the researchers built a predictive model that relates abnormalities in these genes to the progression of the disease. Out of almost 1,500 genes, the researchers were able to select 50 that were the most predictive of Alzheimer’s, according to Stempler, who notes that in Alzheimer’s patients there are either too many or too few of these genes.
When they compared the findings from these 50 genes among Alzheimer’s patients, healthy patients, and primates, including chimpanzees and rhesus monkeys, the researchers discovered that in all but the Alzheimer’s group, the number of the specific genes was tightly limited, with little difference between individuals among each of the species, Stempler explained. This implies that these genes are significant to normal brain functioning, and their strict regulation in healthy patients is compromised by Alzheimer’s disease, she said.
Whether metabolic changes are a cause of the disease or just a symptom remains a topic for future study, she said.
“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,” Stempler said.
The researchers will next try to identify biomarkers in the blood that are associated with these metabolic changes, which may lead to information about the disease’s progression with a blood test, they speculate.
As their work advances, Stempler said she hopes to develop therapeutic strategies that are based around these alterations in the metabolic network to help Alzheimer’s patients, such as medications that can re-introduce strict regulation over gene expression.
The study was published in the journal Neurobiology of Aging.
Source: Tel Aviv University