The search for the holy grail of Alzheimer’s Disease

    29 July 2015

    For scientists investigating Alzheimer’s Disease, a ‘biomarker’ is the holy grail. For example, doctors can test blood for the particular antigen that is associated with prostate cancer. An equivalent for Alzheimer’s would allow doctors to diagnose it at an early stage.

    Currently, a definite Alzheimer’s diagnosis can only be made post-mortem. But there is evidence to suggest that the disease begins to develop long before clinical symptoms manifest, and so the search for an early indicator is crucially important.

    Research published by scientists looking for Alzheimer’s biomarkers at the University of Kentucky’s Sanders-Brown Centre on Ageing reveals the complexity and delicate nature of the search – and helps to explain why progress on Alzheimer’s appears to happen so slowly.

    Professor Mark Lovell has been using unconventional methods to get a more definitive result. Studies have shown that there are altered levels of the proteins tau and beta amyloid in the cerebrospinal fluid of Alzheimer’s sufferers. ‘But a spinal tap to obtain that fluid is often a hard sell for patients,’ Lovell said.

    He began to sort proteins in cerebra spinal fluid by weight, and found that two particular proteins – transthyretin and prostaglandin-d-synthase – ‘fractionate at a higher molecular weight than expected when subjected to oxidative damage.’ Oxidative damage is a key internal driver of Alzheimer’s Disease, although the initial source of the oxidative stress is still unknown.

    Lovell and his team found that these proteins may provide evidence of dysfunction in a region of the brain responsible for the production of cerebrospinal fluid.

    It was found that there was a ‘reasonable correlation’ in cerebrospinal samples and blood taken from the same patients, which means it is possible to determine if the same protein combination appears in blood or urine – which can be taken as samples with far less intrusion than spinal fluid.

    Lovell says that further research is needed before this can be called a definitive success, but adds that if the hypothesis stands up to rigorous testing, ‘we will have a blood based biomarker that might be more predictive than amyloid beta peptide.’