An Open Question: Is the A2A Adenosine Receptor a Novel Target for Alzheimer’s Disease Treatment?

摘要

According to DSM5, the term neurocognitive disorder (NCD) emphasizes that the cause of mental deficit lies in a pathology affecting neuronal circuits. The early clinical stages of NCD (mild-NCD/ MCI) are characterized by functional preservation of everyday activities. Instead, if the disorder has a functional impact it is defined as major-NCD (dementia). On the other hand, the definition of the underlying pathology allows for the etiological classification of NCD (American Psychiatric Association, 2013; Sachdev et al., 2015). Based on the pathological deposition of proteins in brain tissue, NCD due to AD is characterized by a dual proteinopathy in which neurodegeneration is associated with the deposition of amyloid and phosphorylated TAU protein (pTAU). AD is the main age-related degenerative NCD progressively involving memory, complex attention, executive functions, language, and visual-perceptual functions. Personality and behavioural changes are also frequent further complicating the clinical course. On the other hand, due to the late involvement of the movement centers, motor function is usually spared until the most advanced stages of the disease. The AD syndromic evolution reflects the progressive spread of pTAU pathology from the allocortex (entorhinal cortex and hippocampus) to the neocortex (Elahi and Miller, 2017; Hanseeuw et al., 2019).