New frontiers in Alzheimer's disease diagnostic: Monoamines and their derivatives in biological fluids

Current diagnosis of Alzheimer's disease (AD) relies on a combination of neuropsychological evaluations, biomarker measurements and brain imaging. Nevertheless, these approaches are either expensive, invasive or lack sensitivity to early AD stages. The main challenge of ongoing research is therefore to identify early non-invasive biomarkers to diagnose AD at preclinical stage. Accumulating evidence support the hypothesis that initial degeneration of profound monoaminergic nuclei may trigger a transneuronal spread of AD pathology towards hippocampus and cortex. These studies aroused great interest on monoamines, i.e. noradrenaline (NA), dopamine (D) ad serotonin (5-HT), as early hallmarks of AD pathology. The present work reviews current literature on the potential role of monoamines and related metabolites as biomarkers of AD. First, morphological changes in the monoaminergic systems during AD are briefly described. Second, we focus on concentration changes of these molecules and their derivatives in biological fluids, including cerebrospinal fluid, obtained by lumbar puncture, and blood or urine, sampled via less invasive procedures. Starting from initial observations, we then discuss recent insights on metabolomics-based analysis, highlighting the promising clinical utility of monoamines for the identification of a molecular AD signature, aimed at improving early diagnosis and discrimination from other dementia.