Purinergic signaling in cognitive impairment and neuropsychiatric symptoms of Alzheimer's disease

About 10 million new cases of dementia develop worldwide each year, of which up to 70% are attributable to Alzheimer's disease (AD). In addition to the widely known symptoms of memory loss and cognitive impairment, AD patients frequently develop non-cognitive symptoms, referred to as behavioral and psychological symptoms of dementia (BPSDs). Sleep disorders are often associated with AD, but mood alterations, notably depression and apathy, comprise the most frequent class of BPSDs. BPSDs negatively affect the lives of AD patients and their caregivers, and have a significant impact on public health systems and the economy. Because treatments currently available for AD are not disease-modifying and mainly aim to ameliorate some of the cognitive symptoms, elucidating the mechanisms underlying mood alterations and other BPSDs in AD may reveal novel avenues for progress in AD therapy. Purinergic signaling is implicated in the pathophysiology of several central nervous system (CNS) disorders, such as AD, depression and sleep disorders. Here, we review recent findings indicating that purinergic receptors, mainly the A1, A2A, and P2X7 subtypes, are associated with the development/progression of AD. Current evidence suggests that targeting purinergic signaling may represent a promising therapeutic approach in AD and related conditions.

Automated summary

About 10 million new cases of dementia occur globally each year, with up to 70% attributed to Alzheimer's disease (AD). AD patients often experience non-cognitive symptoms known as behavioral and psychological symptoms of dementia (BPSDs), including sleep disorders and mood alterations such as depression and apathy. BPSDs have a significant impact on AD patients, caregivers, public health systems, and the economy. Understanding the role of purinergic signaling, particularly the A1, A2A, and P2X7 receptors, in AD may provide new therapeutic approaches for the disease and related conditions.