DPP-4 inhibitors: a promising therapeutic approach against Alzheimer's disease

Alzheimer's disease (AD), the commonest cause of dementia in ageing adults, is characterized by gradual cognitive impairment and severe functional disability. Key pathophysiological hallmarks involve amyloid-β (Aβ) accumulation, tau hyper-phosphorylation and neuronal loss. Despite extensive basic and clinical investigations, the etiology of the disease remains elusive, although several risk factors have been associated with its development. Current pharmacotherapies including achetylocholinesterase inhibitors and memantine fail to halt disease progression. Interestingly, type 2 diabetes mellitus (T2DM) and AD share several common characteristics, including Aβ deposition, insulin resistance, degeneration, mitochondrial dysfunction, oxidative stress and excessive inflammation. Recent experimental and clinical evidence indicates that dipeptidyl peptidase-4 (DPP-4) inhibitors, being currently used for T2DM therapy, may also prove effective for AD treatment. They may specifically suppress Aβ accumulation, tau hyper-phosphorylation, neuroinflammation, mitochondrial dysfunction and reactive oxygen species (ROS) formation, resulting in the inhibition of cognitive impairment. In this review, we discuss the encouraging current data regarding the molecular and clinical effects of DPP-4 inhibitors in AD, highlighting the need of future studies elucidating their functional role in addressing this incurable disease.