The action of phosphodiesterase-5 inhibitors on β-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 β-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 phosphodiesterase 5 inhibitors (PDE5i) are efficient in reducing the β-amyloid load in hippocampi and improving cognitive decline in rodent models with β-amyloid accumulation. We identified ten original studies, which used rodent models with β-amyloid accumulation, were treated with PDE5i, and β-amyloid was measured in the hippocampi. PDE5i was efficient in reducing the β-amyloid levels, except for one study that exclusively used female rodents and the treatment did not affect β-amyloid levels. Interestingly, PDE5i prevented cognitive decline in all studies. This study supports the potential therapeutic use of PDE5i for the reduction of the β-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 β-amyloid removal in male and female animals.