Identification of Multiple Targets in the Fight against Alzheimer’s Disease

Alzheimer's disease is nowadays one of the most devastating pathologies and a major health and economic issue worldwide. Despite extensive research efforts supported by both public and private funding, an effective treatment is still lacking. While only less than 5% of AD cases is genetically determined, for the major form of disease, defined sporadic AD, we can describe a panoply of risk factors. Indeed, AD is a multi-factorial pathology and probably one of the most complex ones. Being the major hallmarks amyloid plaques and neurofibrillary tangles, research has focused for a long time on trying to eliminate or prevent their formation. The complexity of the cellular mechanisms underlying AD as well as the heterogeneity of its phenotypic manifestations, caused numerous failures in the past. Encouraging pre-clinical results were often not supported when going through clinical trials. Many factors could explain such discrepancies, as the limitations of animal models that reproduce only partially the human pathology and often exaggerate and focus on one particular aspect. If decades ago we thought possible to fight AD focusing on a single universal target, we are currently aware that this was an oversimplification. The complexity of AD manifestations is such that ad personam therapies have been hypothesized and contemporary multiple targets of intervention are considered. Articles disclosing new cellular mechanisms or providing deeper insights into known or novel targets of intervention are multiplying, like in the case of mitochondrial dysfunction and cerebral vascular alterations. Also, a growing body of work points to the involvement of peripheral parameters in AD development, either as triggering events or co-factors. To note, the impact of the microbiome but also the role of inflammation, as well as the contribution of the vascular component have gained interest. We believe that major failures of the approaches developed in the past could be due to the focus on a single parameter. Given the complexity of AD pathology, more comprehensive studies envisioning multiple targets are recommended.

This Research Topic aims to recapitulate the main pathological traits that have now emerged as impacting AD and aims to underline how all these factors are interconnected. Priority will be given to works suggesting novel and/or multi-target approaches. High-standard articles considering a broad range of AD parameters and proposing innovative points of view and targets are encouraged.