Diagnosis and monitoring of Alzheimer Disease with saliva biomarker BACE1

Abstract

Alzheimer’s disease (AD) is characterized by the slow decline of cognition and functional abilities over time. The diagnosis for probable and possible AD relies principally on clinical criteria. The confirmation of the disease is made post-mortem by identifying extracellular senile plaques and intraneuronal fibrillary tangles in the brains of subjects with clinically defined dementia. However, the field critically lacks validated AD specific peripheral biomarkers to support the diagnosis in living patients or for early detection of patients at risk before symptoms appear. BACE1 (Beta site amyloid precursor protein cleaving enzyme 1) cleaves Amyloid Precursor Protein (APP) at two beta sites and represents a key target enzyme in the monitoring and possible treatment of AD. In our preliminary study, we evaluated the usefulness of salivary BACE1 to determine risk to develop AD in clinically normal patients. A preliminary in house laboratory grading system for BACE1 content in saliva was established with high levels of salivary BACE1 present in older patients and putatively at risk to develop AD. BACE1 seems to be a useful biomarker to help diagnose AD and to monitor disease progression, and remarkably regression, when treated with stem cell secretome.