The action of phosphodiesterase-5 inhibitors on ?-amyloid pathology and cognition in experimental Alzheimer?s disease: A systematic review

Alzheimer's disease (AD) is the most frequent cause of dementia worldwide. The etiology of AD is partially explained by the deposition of beta-amyloid in the brain. Despite extensive research on the pathogenesis of AD, the current treatments are ineffective. Here, we systematically reviewed studies that investigated whether phos-phodiesterase 5 inhibitors (PDE5i) are efficient in reducing the beta-amyloid load in hippocampi and improving cognitive decline in rodent models with beta-amyloid accumulation. We identified ten original studies, which used rodent models with beta-amyloid accumulation, were treated with PDE5i, and beta-amyloid was measured in the hippocampi. PDE5i was efficient in reducing the beta-amyloid levels, except for one study that exclusively used female rodents and the treatment did not affect beta-amyloid levels. Interestingly, PDE5i prevented cognitive decline in all studies. This study supports the potential therapeutic use of PDE5i for the reduction of the beta-amyloid load in hippocampi and cognitive decline. However, we highlight the importance of conducting additional experimental studies to evaluate the PDE5i-related molecular mechanisms involved in beta-amyloid removal in male and female animals.

Automated summary

Alzheimer's disease (AD) is the leading cause of dementia worldwide, and the deposition of beta-amyloid in the brain is partially responsible for its etiology. Despite extensive research, current treatments for AD are ineffective. This study systematically reviewed the use of phosphodiesterase 5 inhibitors (PDE5i) in rodent models with beta-amyloid accumulation and found that PDE5i was efficient in reducing beta-amyloid levels in the hippocampi and preventing cognitive decline. However, further experimental studies are needed to evaluate the molecular mechanisms of PDE5i in beta-amyloid removal in both male and female animals.