US Pharm. 2019;44(1):5.

Newly identified changes, say scientists from the University of Eastern Finland, that occur in the brain signal the early stages of Alzheimer’s disease (AD). The researchers employed a multilayered approach to measuring RNA, protein, and phosphorylation levels and performed additional neurobioinformatic analyses on brain-tissue samples from a biobank in Finland. The findings were published in Neurobiology of Disease.

The most common neurodegenerative disease, AD, is identified by the strong accumulation of beta-amyloid peptide and hyperphosphorylated tau protein in brain tissue. In order to find new predictive biomarkers and AD treatment targets, it is important to single out accumulation-induced early changes in the brain. A significant amount of research has explored alterations in RNA gene expression in the brains of patients with AD, but very few studies to date have focused on the total proteome encompassing the entire set of the proteins expressed in cells.

“Yet, we know that changes in expression aren’t always translated to the protein level, and we also know that phosphorylation regulates the function of the proteins produced. Therefore, it is essential to look at multiple levels of regulation at the same time in order to understand the functional changes taking place in the early stages of Alzheimer’s disease,” Postdoctoral Researcher Mikael Marttinen from the University of Eastern Finland explains.

In the clinical study, researchers used data from brain tissue samples categorized according to the accumulation of phosphorylated tau protein, representing the different stages of AD. By undertaking a genome-wide analysis of the samples for alterations in RNA, proteins, and protein phosphorylation, and by analyzing neurobioinformatics, the researchers successfully demonstrated associations of functional changes in certain brain-cell types with AD-related accumulation of phosphorylated tau protein. The scientists also showed that machine learning can be used to classify patients into different stages of disease pathogenesis by simply looking at changes in the expression of selected gene groups.

Subsequent research will explore whether the newly discovered brain changes in various disease stages are also visible in cerebrospinal fluid and blood samples, and whether these might also predict AD. The changes discovered open up new avenues for potential targets of treatment for AD. The scientists also used data from the brain-samples biobank in earlier studies, and the findings have been reported in several leading scientific journals.

For more research on the possible causes of AD and emerging therapies, see this issue’s feature article, “Alzheimer’s Disease: Current Treatments and Potential New Agents” (page 20), by Eric Hoie, PharmD, RPh, et al.

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