Alzheimer’s disease: from basic science to precision medicine approach

Abstract

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. Together with cerebral amyloid accumulation, several factors contribute to AD pathology including vascular alterations, systemic inflammation, genetic/epigenetic status and mitochondrial dysfunction. Much is now being devoted to neuroinflammation. However, anti-inflammatory drugs as numerous other therapies, mainly targeted on β-amyloid, have failed to show efficacious effects in AD. Timing, proper selection of patients, and the need for a multitarget approach appear to be the main weak points of current therapeutic efforts. The efficacy of a treatment could be better evaluate if efficient biomarkers are available. We propose here the application of precision medicine principles in AD to simultaneously verify the efficacy of a treatment and the reliability of specific biomarkers according to individually tailored biomarker-guided targeted therapies. People at risk of developing AD or in the very early phase of the disease should be stratified according to: (1) neuropsychological tests; (2) apolipoprotein E (ApoE) genotyping; (3) biochemical analysis of plasma and cerebrospinal fluid (CSF); (4) MRI and positron emission tomography and (5) assessment of their inflammatory profile by an integration of various genetic and biochemical parameters in plasma, CSF and an analysis of microbiota composition. The selected population should be treated with antiamyloidogenic and anti-inflammatory drugs in randomised, longitudinal, placebo-controlled studies using ad hoc profiles (eg, vascular profile, mitochondrial profile, etc…) If these criteria are adopted widely and the results shared, it may be possible to rapidly develop innovative and personalised drug treatment protocols with more realistic chances of being efficacious.