Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Emergence of the Solution to an Important Unmet Need.

Alzheimer's Disease (AD) represents an increasing problem as the overall population ages. The identification of reliable biomarkers of AD has, therefore, become increasingly important. This is not only for risk prediction and diagnosis in order to provide appropriate care, but also to identify those patients at high risk of AD development who may be eligible for inclusion in clinical trials of novel therapies. Treatment in the early stages of the disease are urgently needed, as these are expected to yield the greatest benefits. The cerebrospinal fluid biomarkers amyloid beta (1-42), hyperphosphorylated Tau and total Tau have been most extensively evaluated. Their combination has been shown to be valuable in identifying AD patients, including those who will progress to AD among a wider group of subjects with only subjective memory complaints or in very early disease stages. While commercially available diagnostic tests for these biomarkers are available, implementation in clinical practice is associated with a number of problems, such as absorption of amyloid beta (1-42) to laboratory tubes, a high degree of batch-to-batch variation with the current test, and the lack of certified reference material. Therefore, there is a need for increased automation and implementation on routine diagnostic platforms in order to support the cost-effective and reliable introduction of the tests on a wider scale. As the use of these biomarkers in research and in clinical practice continues to expand, extensive standardisation efforts are being put in place to address the challenges associated with the use of these biomarkers. Together with the development of additional biomarkers for early and differential diagnosis, this casts good foresight to serve the needs of an increasing patient population.