Neuronal disorders are marked by changes in blood values, which can be used to improve diagnosis. We spoke to Dr Eugenia Wang about her research into developing a blood test to diagnose Alzheimer’s disease, work which will also offer important insights into its progression and development
Advanced Genomic Technology for Alzheimer’s diagnosis
As the most common form of dementia in the world, Alzheimer’s disease is a major global health issue, and with the number of cases set to rise further as life expectancy increases, research into both treatment and diagnosis is an urgent priority. Currently the disease is diagnosed by either a neurological assessment such as the Mini Mental State Examination (MMSE score) or an MRI scan, but now Dr Eugenia Wang is developing a test to diagnose Alzheimer’s by measuring levels of microRNAs in the blood. “microRNAs are tiny molecules that are carried in our bloodstream. Our body has what I would call our equilibrium status, but when something changes suddenly, then our body will reflect this change in the bloodstream,” she explains. Dr Wang says this change in the body’s physiology can be detected. “In the case of a disease situation you can see changes in the plasma of the blood, which are the footprint of the disease process,” she continues. Some individuals start to suffer from mild cognitive impairment (MCI) as they grow older, which is often marked by short-term memory loss. This of course is
www.euresearcher.com
a major concern to the individual affected, but by and large they are still able to live independently; by contrast, cases of Alzheimer’s disease have a far more significant impact. “Alzheimer’s disease cases are characterized by the person starting to lose the ability to perform daily activities, like how to eat and how to bathe,” says Dr Wang. It is thought that people who score less than 24 on the MMSE score are suffering from Alzheimer’s disease, which is then the basis for a more detailed diagnosis. “Then you sub-divide Alzheimer’s patients into three categories; mild is 21-24 on MMSE score, moderate is 10-20, and severe is between 4-9,” outlines Dr Wang. “Not everybody suffering from MCI will convert to bona fide Alzheimer’s disease, but some will. About 15 per cent, annually, convert from MCI to Alzheimer’s disease.”
Oxy-miRs The first objective in Dr Wang’s research was to identify blood differences between Alzheimer’s disease cases and normal controls. Dr Wang and her colleagues have found that this is mainly expressed
through Oxy-miRs, a particular species of microRNA whose functions are associated with oxidative defence. “So far we have identified six types of Oxy-miR (reference at the end of the article) that can differentiate between Alzheimer’s patients and normal elderly controls. We are doing in-depth, large population studies on three of them,” she outlines. Oxy-miRs are a subgroup of microRNAs which functionally suppress the expression of a lot of target molecules, acting almost as a dimmer switch which controls levels of gene expression. “We identified the OxymiR species, made a full gene sequence and put it in a vector, then we put it in a mouse. We’ve made a few transgenic mutant strains, and they now express these same microRNAs, but they overproduce them. So these mice are accelerated in their ageing effects, and are being tested now for the amyloid marker associated with Alzheimer’s. Early data shows us these mice have an accelerated senescent phenotype,” explains Dr Wang. These Oxy-miRs are not solely associated with ageing, however, but also play a key role in the body’s defence
13
