Effect and mechanism of acupuncture on Alzheimer's disease: A review

This comprehensive review examines the effects and mechanisms of acupuncture in the treatment of Alzheimer's disease (AD), a neurodegenerative condition that affects millions of people globally. With the growing aging population, AD represents an urgent medical challenge, especially considering the limitations of current pharmacological treatments. The review analyzes evidence from multiple experimental and clinical studies that demonstrate the therapeutic potential of acupuncture for this devastating condition. The mechanisms of action of acupuncture in AD are complex and multifaceted.

The review highlights that acupuncture acts through modulation of central neurotransmitters, including the cholinergic system, which is critically affected in AD. Studies show that acupuncture can increase the activity of choline acetyltransferase (ChAT) and reduce the activity of acetylcholinesterase (AChE), resulting in greater availability of acetylcholine in the brain. Additionally, acupuncture modulates monoaminergic neurotransmitters such as serotonin, norepinephrine, and dopamine, which are essential for normal cognitive function. A fundamental aspect revealed by the review is the anti-inflammatory role of acupuncture.

Neuroinflammation is a central component of AD pathogenesis, involving microglial activation and release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α. Acupuncture demonstrated the ability to significantly reduce these inflammatory markers, potentially interrupting the vicious cycle of inflammation and amyloid protein deposition. The review also examines the antioxidant effects of acupuncture. Oxidative stress contributes significantly to neurodegeneration in AD, and acupuncture has shown the ability to increase the activity of antioxidant enzymes such as superoxide dismutase (SOD) and reduce lipid peroxidation products such as malondialdehyde (MDA).

These effects are mediated through signaling pathways including Nrf2/ARE, which regulate the cellular antioxidant response. Synaptic neuroplasticity in the hippocampus emerges as a central mechanism through which acupuncture exerts its therapeutic effects. The review documents that acupuncture can improve synaptic plasticity through modulation of proteins related to neuronal growth, including BDNF, GAP-43, and protein kinase C (PKC). These proteins are essential for the formation and maintenance of memories, processes that are severely compromised in AD.

Another important mechanism is the ability of acupuncture to inhibit neuronal apoptosis. Programmed cell death contributes significantly to the neuronal loss characteristic of AD. Studies show that acupuncture can modulate pro- and anti-apoptotic proteins, including the Bcl-2 family, thus reducing neuronal death and preserving cognitive function. The review also addresses the effects of acupuncture on proteins characteristic of AD, particularly amyloid beta (Aβ) protein and hyperphosphorylated tau protein.

Acupuncture has shown the ability to reduce Aβ deposition and decrease tau hyperphosphorylation, two central pathological processes in AD. These effects may be mediated through modulation of kinases such as GSK-3β, which play crucial roles in the processing of these proteins. In terms of clinical application, the review highlights the importance of proper acupoint selection. Points such as Baihui (GV-20), frequently used for brain conditions, and specific point combinations have shown particular efficacy in the treatment of AD.

The intensity and frequency of stimulation are also important factors, with studies indicating that different parameters can produce varied therapeutic effects. Clinical implications are significant. Acupuncture offers a safe, non-pharmacological therapeutic approach that can complement conventional treatments. Its multi-target nature allows simultaneous addressing of several aspects of AD pathophysiology, including inflammation, oxidative stress, neurotransmitter dysfunction, and neuronal death.

This is particularly valuable considering the multifactorial nature of AD. The review also identifies several limitations and future directions. Although preclinical studies are promising, there is a need for more rigorously controlled clinical trials to establish standardized therapeutic protocols. The variability in acupuncture techniques, point selection, and stimulation parameters between studies makes direct comparison of results challenging.

In conclusion, this review presents convincing evidence that acupuncture has multiple beneficial neurobiological mechanisms for AD treatment. Its ability to simultaneously address inflammation, oxidative stress, neurotransmitter dysfunction, and neuronal death makes it a promising therapeutic modality. With ongoing research development and protocol standardization, acupuncture may emerge as a valuable tool in managing this devastating neurodegenerative condition.