Deciphering Alzheimer's disease: predicting new therapeutic strategies via improved understanding of biology and pathogenesis.

INTRODUCTION: There is no cure for Alzheimer's disease (AD). One explanation may pertain to the need to intervene as early as possible upstream from the accumulation of β-amyloid plaques and tau tangles. AREAS COVERED: A PUBMED literature search was completed to review the biological or pathological changes at the basis of disease initiation; this includes neuroinflammation, oxidative stress, microbiome changes and glymphatic system dysfunction. Innovative therapeutic strategies based on these mechanisms are also discussed. EXPERT OPINION: Improved understanding of the pathophysiological mechanisms that underly AD would assist in the identification of drug targets for clinical trials. Furthermore, pharmacokinetic and pharmacodynamic studies are key for the characterization of the properties of disease-modifying drugs and the improvement of their penetration of the blood-brain barrier. Drug targets can be examined at different stages of the disease, hence the importance of selecting and recruiting the appropriate participants, preferably at the earliest stage of AD. New trial designs should be established which primarily involve combination therapies that can work synergistically on common pathways. Going forward, innovative treatment strategies involving nanotechnology, young blood products transfusion and photobiomodulation also offer promise for the future.