Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?

Alzheimer's disease (AD) is a widespread neurodegenerative pathology responsible for about 70% of all cases of dementia. Adenosine is an endogenous nucleoside that affects neurodegeneration by activating four membrane G protein-coupled receptor subtypes, namely P1 receptors. One of them, the A2A subtype, is particularly expressed in the brain at the striatal and hippocampal levels and appears as the most promising target to counteract neurological damage and adenosine-dependent neuroinflammation. Extracellular nucleotides (ATP, ADP, UTP, UDP, etc.) are also released from the cell or are synthesized extracellularly. They activate P2X and P2Y membrane receptors, eliciting a variety of physiological but also pathological responses. Among the latter, the chronic inflammation underlying AD is mainly caused by the P2X7 receptor subtype. In this review we offer an overview of the scientific evidence linking P1 and P2 mediated purinergic signaling to AD development. We will also discuss potential strategies to exploit this knowledge for drug development.

Resistance to the impact of interruptions during multitasking by healthy adults and dysexecutive patients.

Two experiments (one with healthy adult volunteers and the other with controls and dysexecutive patients) assessed the impact of interruptions on a novel test of multitasking. The test involved switching repeatedly between four tasks (block construction, bead threading, paper folding, alphabetical searching) over a 10 min period. In Experiment 1, there were four groups of 20 healthy participants. One group attempted multitasking with no interruption, a second group was interrupted early in the test, a third group late in the test and a fourth group was interrupted both early and late. Interruption involved carrying out a fifth, unexpected task for a period of 1 min before returning to the four main tasks. There was no difference in multitasking performance between the groups. In Experiment 2 the participants were seven dysexecutive patients and 14 age-matched controls. A repeated measures approach was employed to assess the impact of two interruptions (early and late) for both groups. Contrary to predictions, the patients as well as controls were resistant to the effects of interruptions, despite their clearly impaired multitasking performance. These results suggest that the ability to deal with interruptions may be separable from the ability to organise and execute multiple tasks within a limited time frame.