Protein Biomarkers Aid Detection of Prodromal Alzheimer Disease

Cerebrospinal fluid (CSF) biomarkers can predict future development of Alzheimer Disease (AD) dementia within 10 years in patients with mild cognitive impairment (MCI).

The CSF biomarkers, total tau (T-tau), phosphorylated tau (P-tau), and β-amyloid 1-42 (Aβ42), have been compared for their ability to distinguish between early and late converters to AD.

Scientists at Skåne University (Malmö; Sweden) carried out an extended follow-up of the cohort from a previous study involving 137 patients with mild cognitive impairment (MCI) at baseline for an average follow-up period of 9.2 years. Lumbar punctures were performed at base line and during follow up on the 137 patients and 39 human volunteers. They analyzed CSF concentrations of Aβ42, T-tau, and phosphorylated tau P-tau181 using xMAP technology.

Systems using xMAP technology (Luminex; Austin, TX, USA) perform discrete bioassays on the surface of color-coded beads known as microspheres, which are then read in a compact analyzer. The results of the study showed an equal reduction in baseline CSF Aβ42 levels in patients with MCI who converted to AD within five years, the early converters, compared with those who converted later, such as between five and 10 years, whilst T-tau and P-tau levels were substantially higher in early converters compared to later ones. As many as 91% of the patients with mild memory impairment who had these risk markers went on to develop Alzheimer's within a ten-year period. In contrast, those who had memory impairment but normal values for the markers did not run a higher risk of getting Alzheimer's than healthy individuals

By observing how the levels of the biomarkers develop over the ten years before the patient's diagnosis, the scientists have also been able to map the progression of the disease in the brain. The results indicate that it starts with a modified turnover of beta-amyloid. Only later is this followed by changes in the tau protein and damage to nerve cells. This can be important information for those developing new therapies for Alzheimer's. Senior author of the study Oskar Hansson, MD, PhD, said, "This is a very important finding with regard to the development of new therapies against the disease. All prospective therapies have so far shown to be ineffective in stopping the disease, and many people are concerned that the pharmaceutical companies will give up their efforts in this field." The study was published in the January 2012 edition of the Archives of General Psychiatry.

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