Alzheimer's disease: insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases that affect millions of people worldwide, with both prevalence and incidence increasing with age. It is characterized by cognitive decline associated, specifically, with degeneration of cholinergic neurons. The problem of this disease is even more fundamental as the available therapies remain fairly limited and mainly focused on symptoms' relief. Although the aetiology of the disease remains elusive, two main pathological hallmarks are described: i) presence of neurofibrillary tangles formed by unfolded protein aggregates (hyperphosphorylated Tau protein) and ii) presence of extracellular aggregates of amyloid-beta peptide. Given the complexity surrounding the pathogenesis of the disease, several potential targets have been highlighted and interrelated upon its progression, such as oxidative stress and the accumulation of metal ions. Thus, advances have been made on the development of innovative multitarget therapeutical compounds to delay the disease progression and restore cell function. This review focuses the ongoing research on new insights and emerging disease-modifying drugs for AD treatment. Furthermore, classical and novel potential biomarkers for early diagnosis of the disease, and their role in assisting on the improvement of targeted therapies will also be approached.