Luc_2019_Life.Sci_231_116483

Alzheimer's disease (AD) remains one of the greatest global concerns. Current treatment of AD - the acetylcholinesterase inhibitors - provides temporary improvement of cognitive functions, but does not affect the core of the underlying pathological process. There is still the need for alternative approaches, preferably ones based on the upstream events in the AD pathogenesis. The nature of AD pathogenesis remains complicated and not entirely explained. It is assumed to comprise of many interrelated events which can sequentially lead to further pathologies - as a kind of vicious cycle. The solution in this case could be to interact with these processes on multiple levels at the same time. The proposed approach hopes to achieve the state of equilibrium between two pathological pathways via reducing their dynamics on appropriate levels. The first step is to inhibit Tumor Necrosis Factor signaling related to inflammatory response. The second is to take advantage of the influence of insulin signaling on amyloid-beta processing to restore its proper clearance. Employing two only partially-beneficial approaches into a novel approach aims at breaking the "vicious cycle" and eliciting synergistic effect via working on different levels simultaneously. The effect of such therapy could allow physicians to completely inhibit neural damage. The proposed strategy may prove easily introducible as an efficacious clinical approach employing novel anti-TNF agents in combination with anti-diabetic agents. Data is needed on its influence on cognitive functions, any occurrence of adverse effects, and the development of models of optimal doses and their temporal location.