Core Viewpoint - The research highlights the significant role of lithium in Alzheimer's disease, suggesting that lithium deficiency may be a key driver in the early stages of the disease, and proposes potential therapeutic interventions involving lithium supplementation [6][12][16]. Group 1: Alzheimer's Disease Overview - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by severe cognitive impairment, with approximately 60% to 80% of dementia cases attributed to it [1]. - The disease's pathology includes the accumulation of β-amyloid (Aβ) plaques and tau protein tangles, leading to memory and cognitive decline [1][3]. Group 2: Role of Metals in Alzheimer's Disease - Abnormal accumulation of metals such as iron, copper, and zinc in the brains of Alzheimer's patients has been observed, contributing to oxidative stress and promoting Aβ deposition [4][17]. - Lithium, a less studied metal in this context, has shown potential protective effects against Alzheimer's, with lower levels found in the brains of patients [5][6]. Group 3: Lithium's Mechanism and Research Findings - A study published in Nature confirmed that lithium levels decrease in the brains of Alzheimer's patients, and its deficiency can lead to the activation of GSK3β, exacerbating Aβ accumulation and tau phosphorylation [6][11]. - Animal models demonstrated that lithium supplementation could restore memory function and reduce pathological features associated with Alzheimer's [6][10]. Group 4: Potential Therapeutic Approaches - The research identified lithium as a potential intervention for Alzheimer's, with a specific focus on a lithium compound called lithium lactate, which showed promise in reducing Aβ plaques and tau pathology in mouse models [13][16]. - The study emphasizes the need for further clinical trials to evaluate the efficacy and safety of lithium supplementation in humans [16]. Group 5: Dietary Sources and Implications - Dietary sources of lithium include leafy greens, nuts, legumes, and certain mineral waters, suggesting that a diet rich in these foods may help mitigate dementia risk [16].

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].

Core Viewpoint - The recent study from Harvard Medical School suggests that lithium deficiency in the brain is linked to cognitive decline and the onset of Alzheimer's disease, indicating that lithium supplementation, specifically lithium orotate, may reverse memory loss and restore brain health [2][6][9]. Group 1: Alzheimer's Disease Overview - Alzheimer's disease (AD) accounts for 60%-80% of dementia cases, affecting approximately 10% of individuals over 65 years old [2]. - Current FDA-approved antibody therapies for AD have limited effectiveness and potential severe side effects, highlighting the need for alternative treatments [2]. Group 2: Lithium's Role in Cognitive Health - Historical context shows lithium was once promoted as a mood enhancer and later recognized as a standard treatment for bipolar disorder, with epidemiological studies suggesting lower dementia rates in areas with trace lithium in drinking water [5]. - The recent study confirms that lithium is naturally present in the brain and plays a crucial physiological role, with lower lithium levels found in areas affected by Alzheimer's compared to unaffected regions [6]. Group 3: Research Findings - The study found that lithium deficiency leads to increased formation of amyloid plaques in mouse models, creating a vicious cycle where lower lithium levels result in more plaque formation, further exacerbating cognitive decline [6][7]. - Lithium orotate was shown to be more effective than lithium carbonate in reversing Alzheimer's-related brain damage and memory loss in mice, potentially explaining inconsistent results in previous clinical trials [6][9]. Group 4: Implications and Future Research - The study did not find toxic effects associated with lithium supplementation, which could simplify future clinical trials for Alzheimer's treatment [9]. - The potential benefits of lithium may extend beyond Alzheimer's, as higher lithium levels were associated with better performance in memory tests among individuals without cognitive impairment [9].