Nature：锂可逆转老年痴呆

Core Viewpoint - Recent research indicates that supplementing natural lithium levels in the brain may prevent or even reverse Alzheimer's disease [1][5]. Group 1: Research Findings - A study titled "Lithium Deficiency and the Onset of Alzheimer's Disease" shows that decreased lithium concentrations in the brain correlate with memory decline and the neurological features of Alzheimer's, such as amyloid plaques and tau tangles [3][9]. - Experiments on mice reveal that a specific type of lithium supplement can reverse neurological damage and restore memory function, suggesting a potential therapeutic avenue for Alzheimer's [4][12]. - The significance of these findings is profound, as dementia affects over 55 million people globally, with the majority suffering from Alzheimer's [5]. Group 2: Historical Context of Lithium - Historically, lithium has been primarily used in psychiatric medications, particularly for mood regulation and bipolar disorder treatment [7][8]. - Research has shown that lithium users with bipolar disorder experience slower brain aging compared to non-users, leading to investigations into lithium's role in cognitive function maintenance during aging [9]. Group 3: Mechanisms of Action - The study utilized inductively coupled plasma mass spectrometry (ICP-MS) to analyze metal ion homeostasis in Alzheimer's patients, revealing that lithium levels are significantly lower in the prefrontal cortex of mild cognitive impairment (MCI) and Alzheimer's patients [14][20]. - Lithium was found to be the only metal with significantly reduced levels in the brains of MCI and Alzheimer's patients, indicating disrupted lithium homeostasis [23]. - The research also demonstrated that lithium is captured by amyloid deposits, reducing its bioavailability, which may contribute to Alzheimer's pathology [24][31]. Group 4: Effects of Lithium Deficiency - Lithium deficiency accelerated amyloid deposition and tau phosphorylation in Alzheimer's model mice, indicating its critical role in neuroprotection [32][44]. - Behavioral tests showed that lithium-deficient mice exhibited significant learning and memory impairments, further supporting lithium's importance in cognitive function [47][49]. Group 5: Potential Therapeutic Applications - The research team is exploring therapeutic lithium salts with reduced amyloid binding capabilities, which may offer a new treatment strategy for Alzheimer's [100]. - Comparative studies of various lithium salts revealed that lithium acetate (LiO) has lower amyloid binding capacity and effectively reduces amyloid plaque load and tau protein accumulation in mouse models [114][122]. Group 6: Implications for Aging and Cognition - Low-dose lithium treatment in aging mice showed promise in preventing age-related neuroinflammation, synaptic loss, and cognitive decline, suggesting potential benefits for cognitive resilience in older populations [130][133]. - The correlation between endogenous lithium levels and cognitive resilience in aging individuals highlights the importance of maintaining lithium homeostasis for cognitive health [131].