Imagine you’re trying to climb Mount Everest, but every step forward pushes you back two steps. That’s what it feels like for scientists developing drugs to treat Alzheimer’s disease. AD, the most common neurodegenerative disease, brings forth cognitive and mental challenges that burden patients and their families. Although current drugs provide some relief, they only delay the disease’s progression. To understand why drug development is so tricky, researchers have examined the abnormal protein deposition, decreased brain activity, and inflammatory reactions in AD. Despite recent approval of aducanumab, its long-term effects remain uncertain. This literature review explores new therapeutic strategies and focuses on anti-Aβ and anti-tau drugs, mitochondria-targeting, and multi-target approaches. It also highlights the challenges faced during drug development. So buckle up and dive into this article to learn about cutting-edge ways scientists are battling the bottlenecks and paving the way for future drug therapies against Alzheimer’s disease!

Alzheimer’s disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients’ families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aβ), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aβ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.

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