Astrocyte reactivity modifies the effects of locus coeruleus norepinephrine-related dysfunction on tau and its impact on cognition.

Mild cognitive impairment (MCI) is characterized as an intermediary condition between normal aging and Alzheimer disease (AD), wherein individuals experience memory deficits that exceed the normative expectations for their age, alongside varying degrees of impairments in other cognitive functions; however, these symptoms do not significantly disrupt daily living activities []. Recent epidemiological research suggests that the estimated overall prevalence of MCI in China is approximately 15.5% []. As the aging population in China continues to expand, there has been a significant rise in the prevalence of MCI. MCI encompasses several subtypes, with the most prevalent being amnestic mild cognitive impairment (aMCI) []. Distinct from other subtypes, aMCI is primarily characterized by a significant decline in memory function [], which serves as its principal clinical manifestation. This feature renders it more closely associated with AD and makes it the subtype most susceptible to conversion into AD []. A study conducted among a random sample of 3246 older Chinese community members revealed that the prevalence of aMCI was 17.1%, with an annual incidence rate of 70.57%. Furthermore, the conversion rate from aMCI to AD in the absence of intervention ranged between 10% and 17% []. The most salient manifestations of AD include significant memory deficits, alongside cognitive deterioration, visual-spatial dysfunction, executive function impairment, and neuropsychiatric symptoms that are independent of cognitive processes []. These symptoms collectively contribute to a deterioration in the capacity for independent living and a significant impairment of self-care abilities, thereby profoundly impacting the quality of life as well as the physical and mental health of older adults. aMCI is regarded as a preliminary phase of AD, and identifying effective treatment strategies for aMCI holds significant clinical implications for the prevention of AD. At present, the management of aMCI predominantly relies on pharmacological interventions, with the medications used frequently mirroring those used in AD treatment strategies, including donepezil, memantine, and cholinesterase inhibitors [,]. Nevertheless, research has demonstrated that these medications not only fail to impede the progression of aMCI to AD but also induce adverse effects during their administration []. Therefore, there exists an urgent clinical demand for a safer alternative treatment with reduced side effects for individuals diagnosed with aMCI. Acupuncture is a traditional Chinese medical practice and one of the primary modalities for disease treatment within traditional Chinese medicine. It is considered safe, exhibits minimal side effects, and demonstrates significant long-term efficacy. Acupuncture has demonstrated potential efficacy in ameliorating mild cognitive impairment and enhancing memory, positioning it as a viable complementary and alternative therapy [,]. Our prior animal studies have demonstrated that acupuncture can enhance memory and alleviate cognitive impairments in AD mouse models, thereby offering a substantial experimental foundation [,]. Gold Needles, primarily composed of gold, are used in acupuncture treatments due to their advantageous properties. In comparison to other metallic materials, gold exhibits more stable chemical characteristics and a softer texture, facilitating precise control over penetration direction while minimizing discomfort for patients []. In clinical practice, the therapeutic efficacy of Gold Needles for a range of conditions, including neurological disorders, surpasses that of conventional metal needles []. Currently, there is a paucity of high-quality clinical trials investigating acupuncture treatment for aMCI, and no clinical studies have been conducted on Gold Needle intervention for this condition. Therefore, it is imperative to undertake relevant clinical investigations. The onset of aMCI is insidious, and certain symptoms may not be readily apparent, rendering them susceptible to oversight. As an early manifestation of AD, aMCI exhibits numerous similarities with AD []. The precise mechanisms underlying the development of aMCI remain unclear, and numerous hypotheses have been proposed to elucidate this phenomenon. aMCI is predominantly characterized by the development of senile plaques formed from beta-amyloid (Aβ) protein deposits, alongside the accumulation of tau-related proteins that give rise to neurofibrillary tangles []. In light of the clinical symptoms and pathological characteristics associated with aMCI, this trial incorporates a comprehensive approach that includes neuropsychological assessments, cognitive function evaluations, imaging analyses, and molecular biological investigations to assess the efficacy and safety of the Gold Needle “regulating the spirit” method in treating aMCI.