MPI Research’s director of immunology Yi Qun Xiao, and senior manager of biomarkers and immunoassay development Mark Cameron look at how to generate more focused and reliable clinical results for the treatment of Alzheimer’s.

Biomedical research continues to unravel the mysteries of Alzheimer’s disease. Of the six leading killer diseases in the US, all but one experienced declining death rates from 2000-08. Alzheimer’s was the exception, with a 66% rise in mortality. In 2010, Alzheimer’s Disease International estimated the number of people with dementia, primarily Alzheimer’s, at 36 million worldwide – a figure expected to triple by 2050 – and the cost of care at $604bn, or 1% of global gross domestic product.

New insights from the study of specific biomarkers, including a protein that can be objectively measured as an indicator of a normal or disease state process, suggest new research targets. While the underlying mechanisms of Alzheimer’s remain elusive, scientists are learning more, including ways to detect it at the earliest stage through the study of key biomarkers.

In the research arena, early detection can improve our understanding of disease progression – a crucial element in developing useful treatments – while identifying the most at-risk candidates for clinical trials. At the patient level, early detection allows patients and physicians to determine the most effective course of care as soon as possible.

In 2010, the number of people with dementia, primarily Alzheimer’s, was estimated at 36 million worldwide and the cost of care at $604bn."

Recent studies indicate an Alzheimer’s-related connection between two biomarkers in cerebral spinal fluid: Amyloid-beta (A-beta) 42 and Tau. Researchers at the University of California, San Diego School of Medicine found that onset of Alzheimer’s symptoms required A-beta plaque deposits and elevated levels of a Tau protein known as p-Tau.

The levels of Tau and A-beta 42 in cerebral spinal fluid are statistically different between Alzheimer’s patients and those without the illness. Measuring these levels can distinguish Alzheimer’s from other conditions, such as age-related memory impairment, depression and some secondary dementias.

By analysing these biomarkers, scientists have a new tool for understanding the neurodegenerative progression of Alzheimer’s at the earliest stage. It also has potential for developing drug therapies that target A-beta 42 and Tau protein regulation sooner, thereby assessing potential efficacy of a drug candidate.

Setting down a marker

MPI Research has validated A-beta 42 (see Figure 1) and Total Tau (see Figure 2) immunoassays on its Sector Imager platform from meso scale discovery (MSD). These immunoassays are a particularly effective means of measuring biomarkers in cerebrospinal fluid.

The MSD system is based on MULTI-ARRAY technology, a proprietary combination of electrochemiluminescence detection and patterned arrays, for rapid detection and high throughput, an expanded dynamic range, and capability with single and multiplex assay formats. The A-beta 42 and Total Tau assays were validated in accordance with a white paper on biomarker fit-for-purpose methods and executed following GLP regulatory requirements.

"MPI Research anticipates a bigger role for biomarkers in the development of treatments for Alzheimer’s."

MPI Research anticipates a bigger role for biomarkers in the development of treatments for Alzheimer’s. Because of the relationship between A-beta 42 and Tau, precise immunoassays will be useful in better defining patient groups for trials, including the identification of asymptomatic individuals at high risk of eventual neurodegenerative and cognitive decline.

This should lead to more focused and reliable clinical results, faster progress of promising therapies and reduced drug development costs.