BACE1 as a potential biomarker for Alzheimer's disease

The diagnosis of Alzheimer's disease (AD) relies principally on clinical criteria for probable and possible AD as defined by the NINCDS-ADRDRA. The field is desperately lacking of biological markers to assist with AD diagnosis and verification of treatment efficacy. According to the Consensus Report of the Working Group on Molecular and Biochemical Markers of Alzheimer's Disease, in order to qualify as a biomarker the sample in question must adhere to certain basic requirements, including the ability to: reflect AD pathology and differentiate it from other dementia with an 80% sensitivity; be reliable and reproducible; be easy to perform and analyze; remain relatively inexpensive. Beta secretases are crucial enzymes in the pathogenesis of AD. Given its primary role in brain amyloidogenesis and its ubiquitous expression, one may consider measuring peripheral BACE1 levels and activity as biomarkers of AD, like performed in the brain and cerebrospinal fluid. However, very little is known about the periphery and whether peripheral BACE1 is involved in AD pathogenesis or mirrors AD progression. Moreover, no investigation has focused on the possibility of monitoring peripheral BACE1 to assess the efficiency of BACE1 inhibitors during the course of clinical trials. Part of the problem may be attributed to the lack of sensitive molecular tools which are absolutely necessary to use BACE1 as a biomarker. In this review we evaluate the progress and feasibility of developing BACE1 as a biomarker for AD in different tissues.