06 May 2011

A breakthrough in the diagnosis of Alzheimer's disease?

Blood test for Alzheimer's disease: differential diagnosis at an early stage of the disease
LifeSciencesToday based on the materials of McGill University Health Centre: Blood Test for Alzheimers

Thanks to an innovative study conducted by the Research Institute of the McGill University Health Center (MUHC), a new blood test for the diagnosis of Alzheimer's disease may soon appear on the market. The development of a unique biochemical analysis that identifies patients with this neurodegenerative disease has become possible thanks to the study of the formation of the brain hormone dehydroepiandrosterone (DHEA) during the oxidation of blood serum.

The results of the work, which is important for millions of sufferers of this disease, are published in the Journal of Alzheimer's Disease: Rammouz et al., A Lead Study on Oxidative Stress-Mediated Dehydroepiandrosterone Formation in Serum: The Biochemical Basis for a Diagnosis of Alzheimer's Disease.

"There is still no diagnostic tool for Alzheimer's disease that provides unambiguous data, except for postmortem analysis of brain tissue," says senior author of the article Dr. Vassilios Papadopoulos, director of the MUHC Research Institute. "Our clinical studies have shown that a non-invasive blood test based on a biochemical process can be successfully used to diagnose Alzheimer's disease at its early stage, which also makes it possible to distinguish it from other types of dementia."

The test developed by Dr. Papadopoulos and his colleagues is based on the formation of the hormone dehydroepiandrosterone (DHEA) (dehydroepiandrosterone, DHEA). High levels of this hormone are noted in the brain, where it has a wide range of biological effects.
Previously, scientists identified a brain- and cell-specific mechanism of dehydroepiandrosterone biosynthesis mediated by oxidative stress in the brains of rats, bulls and humans. This alternative pathway is induced by pro-oxidant substances such as Fe2+ and beta-amyloid peptide. Using brain tissue samples obtained from controls and from patients with Alzheimer's disease, they obtained evidence that dehydroepiandrosterone is formed in the brains of patients with Alzheimer's disease as a product of oxidative stress-mediated metabolism of an unknown precursor, which reduces the levels of this precursor in the blood.

The researchers tested the presence of this DHEA precursor in human serum using a simple Fe2+-based reaction and determined the amount of DHEA formed. Of the 86 individuals included in the study, 19 men and 20 women suffered from Alzheimer's disease; 18 men and 22 women of the corresponding age formed the control group; 4 men and 3 women had moderate cognitive impairment. Serum oxidation led to a sharp increase in DHEA levels in the control group, while in the serum of patients with Alzheimer's disease, the increase in levels was either not observed or was insignificant.

Changes in the level of dehydroepiandrosterone after serum oxidation correlated with the cognitive and mental state of patients. These results showed that comparing the serum levels of DHEA in patients before and after oxidation can be a useful tool for the diagnosis of Alzheimer's disease.

"There is a clear correlation between the inability to obtain DHEA by blood oxidation and the degree of cognitive impairment accompanying Alzheimer's disease," Papadopoulos says. "We have shown that it is possible to accurately and repeatedly diagnose Alzheimer's disease based on small blood samples. This analysis also allows for differential diagnosis of the early stages of Alzheimer's disease, which means that it can be used as a test for this disease at its very beginning."

"There are many promising methods of treating Alzheimer's disease, the target of which are the main mechanisms of the development of this disease, currently undergoing clinical trials," Papadopoulos adds. "However, the realization of the potential of any therapy method depends on the reliability of the diagnosis."

Currently, when making a diagnosis of Alzheimer's disease, family history is investigated, mental state assessment and physical tests are carried out, in which special attention is paid to neurological symptoms.

"An accurate, early and specific non-invasive biochemical test correlating with clinical data is vital. We believe that our results show that the test for the formation of dehydroepiandrosterone by blood oxidation can be used to diagnose Alzheimer's disease at its earliest stage and to monitor the effectiveness of therapy and disease progression."

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