The Therapeutic Efficacy of Gold Needle "Regulating Spirit" Acupuncture for Amnestic Mild Cognitive Impairment: Protocol for a Randomized Controlled Trial.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of beta‐amyloid (Aβ) plaques, tau neurofibrillary tangles, and progressive cognitive decline.The pathophysiology of the disease begins years before the onset of cognitive symptoms, marking its long preclinical phase.Autopsy studies suggested that the locus coeruleus (LC), a small pontine nucleus, is one of the earliest brain regions to harbor hyperphosphorylated tau (p‐tau), long before tau and Aβ appear in the cortex.The LC is the brain's primary source of norepinephrine (NE), which is released throughout the brain through the LC's long and diffuse projections in response to novelty, high arousal, and cognitively demanding tasks.NE plays a crucial role in modulating brain network activity and supports many cognitive and behavioral functions that are impaired early in AD, such as learning and memory., , NE also provides neuroprotection against AD‐related neuroinflammatory processes by downregulating microglial function and the transcription of pro‐inflammatory genes in astrocytes., Indeed, lesioning the LC in rodents was linked to cortical NE depletion and astrogliosis,which in turn resulted in reduced Aβ clearance and impaired learning and memory,suggesting a causal relationship between LC dysfunction and astrocyte reactivity‐related disease progression in AD. : Literature database searches revealed evidence from animal work suggesting that astrocyte reactivity is a critical upstream factor linking pharmacologically induced locus coeruleus (LC)–norepinephrine (NE) system dysfunction and cortical AD pathology. Autopsy studies indicate that the LC is among the earliest regions to accumulate AD‐related tau pathology in humans. Here, we examined whether astrocyte reactivity also plays a modulatory role in the relationship between LC dysfunction and tau, or in its downstream cognitive sequelae in humans.