Acupuncture for the Treatment of Alzheimer's Disease by Targeting the Autophagy-Lysosome Pathway: A Systematic Review

Zitong Feng ¹ Yuexi Lin ¹ Zhihao Luo ¹ Yutong Zhou ¹ Siqin Li ¹ Dongmin Liu ¹ Shaoyang Cui ^2* Chunzhi Tang ^1*

• ¹ Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China
• ² Shenzhen Hospital (Fu Tian) of Guangzhou University of Chinese Medicine, Shenzhen, China

Objective: This study aims to investigate whether acupuncture can improve cognitive function in Alzheimer's disease (AD) animal models by targeting the autophagylysosome pathway (ALP) and its underlying mechanisms through a systematic review.The following databases were searched from inception until August 2024: PubMed, Web of Science, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wangfang database. Animal studies assessing the impact of acupuncture on ALP in AD were included. The primary outcomes were ALP-related outcome, including autophagy, lysosomal function, and autophagic flux and behavioral tests. Methodological quality was evaluated using the SYRCLE RoB tool.Results: A total of 11 studies with a total of 282 mice or rats were included. The included studies suggested that acupuncture improved the cognitive ability of AD models according to the improvement of the behavior tests including Morris Water Maze and Fear Conditioning tests. Moreover, Acupuncture may modulate ALP in AD models, as evidenced by western blot, immunofluorescence, and transmission electron microscopy findings. The mechanism could involve the inhibition of AKT, MAPK, and mTORC1, as well as the activation of AMPK, leading to the activation of TFEB and TFE3, and/or the bidirectional regulatory role of acupuncture on autophagy in a context-dependent manner.Preliminary evidence suggests that acupuncture may influence ALP in AD models, improving cognitive impairment. However, further high-quality animal trials and clinical studies are needed to confirm these effects.