Alzheimer’s Disease: Original Mechanisms and Translational Impact

Over the last years, several international scientific journals focused their attention on Alzheimer’s disease (AD), the most common neurodegenerative disorder and the first cause of admission to medical nursing homes in the elderly. Among the most important issues that underwent an important revision thanks to the scientific evidence accumulated worldwide is the pathogenetic role of amyloid-β-peptide (Aβ): earliest studies considered fibrillar Aβ responsible for neuronal death and the following cognitive loss, whereas recent preclinical and clinical observations supported the hypothesis that an imbalance between the synthesis and clearance of soluble Aβ plays a major role in neurodegeneration. In particular, soluble Aβ has been reported to be involved in synaptic loss and cognitive decline. Another topic still under critical revision is the clinical impact of AD-associated mood disorders, in particular anxiety and depression, frequent co-morbidities in people suffering from AD. Indeed, an overproduction of soluble Aβ has been demonstrated to have a role in the onset of depression. Quite important is to underlie the failure of drug research and development to provide AD patients with novel drugs able to slow the progression of the disease and improve cognitive skills. Despite their efficacy in preclinical settings, many drugs resulted unsuccessful when tested in AD patients in terms of amelioration of memory functions or implementation of the ability to carry out the activities of daily living.

In this Research Topic we would like to outline the multi-factorial etiology of AD and on promising key factors for the development of new and successful therapeutic strategies. In particular, we will collect recent research on early regulatory signals, levels of disease markers as well as on the interplay between novel molecular mechanisms, including neurotransmitter dysfunctions and synaptic failure, enzymes dysregulation, oxidative and neuroinflammatory events, cytoskeletal destabilization, metal ion and vitamin deficiency. A qualifying and outstanding aspect of this Research Topic would be also the evaluation of extra-neural effect of Aβ accumulation in order to address the involvement of brain damage in systemic amyloidosis.

In this Research Topic we will welcome Original Research article, Review or Mini Review, Case Report, Data Report, General Commentary, Brief Research report and Opinion articles.