Alzheimer’s Disease (AD) is a devastating neurodegenerative disease that is difficult to definitively diagnose anti-mortem. It is often mistaken in the early stages for simply “getting old”. At later stages it is easily confused for other dementias with similar presentation but different pathology. Traditionally it has been a rule-out rather than a rule-in approach.

Post-mortem AD is characterized by neurofibrillary tangles of Tau protein and plaques of Amyloid Beta (Abeta) peptides. Due to this many groups have looked at using Abeta 1-42 and Tau protein as biomarkers in CSF and potentially plasma to help diagnose the disease. More recently the advent of PET scan reagents for Abeta and now Tau have helped quantitate the protein and peptide load in the brain and correlate with disease state. However, these are expensive procedures with x-ray exposure.

There are many groups working on therapies for AD and their results have been mixed. Part of this is due to the difficulty to ensure that patients in the control group are not in the prodromal stage of AD and that patients in the disease group do not have a different dementia to AD. Further once a therapy is developed a diagnostic test will be needed to identify patients needing intervention and for monitoring of them.

To this end I will discuss the road to developing and commercializing a mass spectrometry based Abeta 1-42/1-40 ratio CSF assay with clinical trial and the subsequent development of an Abeta 1-42/1-40 ratio plasma-based screen with clinical trial. The various phases and challenges along the way will be discussed and the read-out data shown. Both tests are now being used in patient care and clinical trial enrollment. With several therapies in phase IIb or III the need for such well clinically characterized assays is growing.