Understanding the role of microglia in Alzheimer's disease: insights into mechanisms, acupuncture, and potential therapeutic targets

doi:10.19852/j.cnki.jtcm.20250327.002

Abstract

Abstract:

Microglia (MG) are immune effector cells in the central nervous system (CNS) and play a pivotal role in the pathogenesis of various CNS diseases. Alzheimer's disease (AD) is defined as a severe chronic degenerative neurological disease in humans. The amyloid cascade hypothesis is a hypothesis on the pathogenesis of AD that suggests that abnormal extracellular aggregation of β-amyloid (Aβ) peptides is the main cause of the disease. Although this hypothesis has been found to be convincing, a growing body of evidence suggests that it does not fully explain the pathogenesis of AD. Neuroinflammation is a crucial element in the pathogenesis of AD, as evidenced by elevated levels of inflammatory markers and the identification of AD risk genes associated with innate immune function. This paper will first summarize the impact of microglia-mediated neuroinflammation on AD, exploring the phenotypic changes that follow microglia activation. Secondly, the interactions between microglia, Aβ, microtubule-associated protein, apolipoprotein E and neurons are thoroughly investigated, with particular focus on the interactive mechanisms. Furthermore, the recent progress and prospects of microglia as a diagnostic and therapeutic target for AD are analysed. A review of the literature on the mechanisms regulating MG for AD at home and abroad revealed that acupuncture modulation of microglia could help to delay the progression of AD. This was followed by an extensive discussion of the clinical possibilities and scientific validity of acupuncture treatment for AD, with the aim of providing new insights for acupuncture modulation of MG targeting for the treatment of AD.

Key words: microglia, Alzheimer disease, acupuncture, therapeutic targets, review

JIANG Jinglei, YU Tao, QIAN Yulin, WANG Meng. Understanding the role of microglia in Alzheimer's disease: insights into mechanisms, acupuncture, and potential therapeutic targets[J]. Journal of Traditional Chinese Medicine, 2025, 45(4): 922-936.

Figures/Tables 5

Table 1 Progress of research on AD diagnostic criteria

Individual/organization	Event	Description
Alois Alzheimer (1864)¹¹	Publication of AD case report	The clinical manifestations and pathological features of AD
NINCDS-ADRDA (1984)¹²	Release of NINCDS-ADRDA diagnostic criteria	The first widely accepted diagnostic criteria for AD
NIA (1997)¹³	Proposal of NIA-Reagan criteria	Emphasized the importance of pathological diagnosis.
NIA-AA (2007)¹⁴	Introduction of new diagnostic criteria	First introduction of biomarkers for diagnostic assistance.
NIA-AA (2011)¹⁷	Update of NIA-AA criteria and ABC framework	Proposed the "ABC" diagnostic framework, dividing diagnosis into preclinical, MCI, and clinical stages.
NIA-ADRD (2018)¹⁵	Joint release of "New Research Framework for Alzheimer's Disease"	Emphasized the importance of biomarkers and differentiation from dementia.
IAWG (2021)¹⁶	Release of updated diagnostic guidelines	Emphasized personalized diagnosis and treatment, and added more biomarkers for diagnosis.

Figure 1 Microglia influence neurons by modulating neuroinflammatory responses and are associated with Aβ, tau, NFTs, and cognitive function DAM: disease-associated microglia; TREM2: triggering receptor 2; IL-21: interleukin-21; IL-10: interleukin-10; IL-6: interleukin-6; TGF-β: transforming growth factor-β; Arg-1: arginase-1; NF-κB: nuclear factor kappa B. This figure was generated by Figdraw (Hangzhou Duotai Technology Co., Ltd., Hangzhou, China).

Figure 2 Interaction mechanisms between microglia and APOE, along with the modulation of microglia to improve cognitive function LDLR: low-density lipoprotein receptor-associated protein 1; IFN-γ: interferon-γ; NFTs: neurofibrillary tangles; mTOR: mammalian target of rapamycin; LRP1: low-density lipoprotein receptor-related protein 1; ABCA1: ATP-binding cassette subfamily A member 1; HSPG: heparan sulfate proteoglycans. This figure was generated by Figdraw (Hangzhou Duotai Technology Co., Ltd., Hangzhou, China).

Figure 3 Pathological mechanism of microglia in AD TNF-α: tumour necrosis factor-α; IL-1β: interleukin-1β; TGF-β: transforming growth factor-β; IL-10: interleukin-10; LDLR: low-density lipoprotein receptor; LRP1: low-density lipoprotein receptor-related protein 1; APOE: apolipoprotein E; Aβ: amyloid. This figure was generated by Figdraw (Hangzhou Duotai Technology Co., Ltd., Hangzhou, China).

Figure 4 Acupuncture reduces pathological accumulation and improves cognition in AD rats APOE: Apolipoprotein E; Aβ: amyloid; Yingxiang: (GV26); Hegu: (LI4); Fengfu: (GV15); Baihui: (GV20); Naohu: (GV16); P-tau: phosphorylated tau protein; APOE4: apolipoprotein E4. This figure was generated by Figdraw (Hangzhou Duotai Technology Co., Ltd., Hangzhou, China).

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