Core Findings - A team from the University of California, Irvine discovered that a combination of Vitamin B3 (niacinamide) and the active component in green tea, EGCG, can rejuvenate aging brain cells and effectively clear harmful protein accumulations associated with Alzheimer's disease [1][2] - The research published in the latest issue of "Aging Science" indicates that this combination significantly enhances the levels of GTP, a key energy molecule in brain cells, and improves the ability to clear β-amyloid proteins, which are characteristic of Alzheimer's disease [1][3] Mechanism of Action - The study utilized a gene-encoded fluorescent sensor named GEVAL to monitor GTP dynamics in neurons of aged Alzheimer's model mice, revealing a continuous decline in GTP levels with age, particularly in mitochondria, which severely impacts autophagy, the process of clearing damaged components [1] - Neurons treated with niacinamide and EGCG showed GTP levels restored to those of younger cells, leading to improved energy metabolism, activation of key proteins responsible for cellular transport, and efficient clearance of β-amyloid aggregates, thereby reducing oxidative stress associated with neurodegeneration [2] Implications for Treatment - The findings suggest that the combination of these two natural dietary supplements may serve as a new tool in combating cognitive decline and Alzheimer's disease [3]

Core Viewpoint - The research on Alzheimer's disease (AD) has shifted focus from the traditional view of amyloid-beta (Aβ) accumulation and tau protein tangles as the primary causes of dementia, highlighting the role of dysfunctional microglia and chronic neuroinflammation in disease progression [2][3]. Group 1: Research Findings - Recent studies indicate that abnormal protein deposition is a pathological feature of AD rather than its causative mechanism, emphasizing the harmful effects of these proteins on disease progression [2]. - The study published by Xu Peisheng's team at the University of South Carolina introduces a ceria nanocluster-based therapy that targets activated microglia and reduces Aβ deposition [3][4]. Group 2: Innovative Treatment Approach - The developed brain-targeted ceria nanoparticles (T-CeNP) effectively penetrate the blood-brain barrier (BBB) and alleviate neuroinflammation while reducing Aβ accumulation [4][6]. - T-CeNP operates through a triple-function mechanism: it crosses the BBB via RAGE-targeting peptides, regulates pathological processes by enhancing microglial phagocytosis of Aβ, and exhibits multi-pathway synergistic effects in AD mouse models [6][7]. Group 3: Implications for Future Research - The study's findings suggest that T-CeNP can effectively block the pathological cascade of Alzheimer's disease by modulating the neuroinflammatory microenvironment and amyloid metabolism, providing a new paradigm for multi-target therapies in neurodegenerative diseases [9].

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 - Alzheimer's disease (AD) is a severe neurodegenerative disorder with significant impacts on individuals and society, yet drug development has faced numerous failures despite substantial investments from major pharmaceutical companies [2][3]. Drug Development and FDA Approvals - In June 2021, the FDA accelerated the approval of Aducanumab, developed by Eisai and Biogen, marking the first new drug for Alzheimer's since 2003, although its approval was controversial due to associated risks like ARIA (Amyloid-related Imaging Abnormalities) [3][6]. - Following Aducanumab, the FDA approved two additional antibody drugs targeting Aβ: Donanemab by Eli Lilly and Lecanemab by Eisai and Biogen, both of which also present ARIA-related side effects [3][6]. Denali Therapeutics' Research - Denali Therapeutics published a study in August 2025 on a new antibody transport carrier, ATV cisLALA, which utilizes transferrin receptor (TfR) to enhance brain delivery of anti-Aβ antibodies while mitigating ARIA risks [4][9]. - The ATV cisLALA carrier shows improved distribution in brain tissue compared to traditional Aβ antibodies, which tend to accumulate around blood vessels, potentially triggering inflammatory responses and ARIA [9][11]. Mechanism of Action - Traditional Aβ antibodies enter the brain through cerebrospinal fluid and perivascular spaces, where amyloid deposits are located, leading to inflammation and ARIA. In contrast, the ATV carrier enhances delivery through capillaries, reducing ARIA side effects [11][12]. - Denali's TfR-based approach is not limited to Aβ; the company is also developing therapies targeting tau protein using the same delivery mechanism, aiming to address two key toxic proteins in Alzheimer's simultaneously [11].

Core Viewpoint - The study highlights the importance of understanding the epigenomic mechanisms underlying Alzheimer's disease (AD) progression and cognitive resilience, suggesting potential new intervention strategies to delay cognitive decline [3][10]. Group 1: Research Overview - The research published in the journal Cell explores the epigenomic rewiring in Alzheimer's disease progression and cognitive resilience, utilizing single-cell multi-region epigenomic and transcriptomic techniques [4][10]. - A total of 111 individuals were selected for the study, including 57 non-AD, 33 early-stage AD, and 21 late-stage AD patients, covering six brain regions [7]. Group 2: Key Findings - The study identified over 1 million cis-regulatory elements and defined 123 functional modules, revealing cell-type specific associations with genetic risk factors for Alzheimer's disease and other brain disorders [7][8]. - It was found that there is a widespread phenomenon of "epigenomic information loss" in the brains of Alzheimer's patients, correlating with the functional decline of neurons and glial cells [8]. Group 3: Cognitive Resilience Insights - The research elucidated the epigenomic basis of cognitive resilience, showing that individuals with stronger cognitive resilience maintain higher levels of epigenomic information in key cell types [9]. - The study suggests that the stability of the epigenome is a critical molecular mechanism supporting cognitive resilience, providing new avenues for enhancing cognitive function and delaying Alzheimer's disease progression [9][10].

Core Viewpoint - The article highlights significant research published in the journal Cell, with a focus on groundbreaking studies from Chinese scholars in various fields, including Alzheimer's disease treatment, cartilage regeneration, and innovative RNA-protein interaction technologies [2]. Group 1: Alzheimer's Disease Research - A study by researchers from Gladstone Institutes and UCSF identified two FDA-approved cancer drugs, letrozole and irinotecan, that can reverse gene expression changes associated with Alzheimer's disease, significantly improving memory and reducing pathological features in a mouse model [4][7]. Group 2: Cartilage Regeneration - Research from Tongji University and Hainan Medical University discovered Procr+ chondroprogenitors that are sensitive to mechanical stimuli, crucial for maintaining cartilage homeostasis and promoting regeneration after joint injury, indicating potential for treating knee diseases like osteoarthritis [9][12]. Group 3: Prime Editing for Neurological Disorders - The Broad Institute's study demonstrated the use of prime editing technology in mice to correct common ATP1A3 gene mutations associated with alternating hemiplegia of childhood, leading to significant improvements in clinical symptoms and lifespan [14][17]. Group 4: RNA-Protein Interaction Technology - A new RNA-binding protein identification technique called SPIDR was developed, allowing for the analysis of multiple RNA-binding proteins' binding sites, which could enhance understanding of RNA biology and mechanisms of translational suppression under cell stress [19][21]. Group 5: Post-Stroke Brain Inflammation - Research from Johns Hopkins University revealed that the mast cell receptor Mrgprb2/MRGPRX2 mediates brain inflammation after a stroke, and inhibiting this receptor can reduce inflammation and improve neurological outcomes in mice [23][25]. Group 6: Aging Proteome Atlas - A comprehensive study by the Chinese Academy of Sciences constructed a proteome aging atlas across a 50-year lifespan, identifying aging trajectories and key proteins like GAS6 that drive vascular and systemic aging [27].

Core Viewpoint - The article emphasizes the detrimental effects of a sedentary lifestyle, highlighting that just ten days without exercise can lead to significant metabolic and cognitive decline, including insulin resistance and memory impairment [6][12]. Group 1: Impact of Sedentary Lifestyle - A study led by Dr. Nathan Kerr from the University of Missouri reveals that ten days of inactivity can accelerate insulin resistance and negatively affect memory function [6]. - The research involved a hindlimb immobilization experiment on four-month-old female Wistar rats, demonstrating that lack of exercise triggers a "degenerative storm" in both the body and brain [6][8]. Group 2: Cognitive Decline Mechanisms - The hippocampus shows signs of insulin resistance after just ten days of inactivity, disrupting glucose metabolism and leading to mitochondrial dysfunction and increased reactive oxygen species (ROS) [8][9]. - Abnormal levels of amyloid precursor protein (APP) and tau protein, markers for Alzheimer's disease, were observed, indicating a potential risk for cognitive decline [9]. Group 3: Iron Metabolism Imbalance - The study found that muscle inactivity leads to abnormal iron accumulation in muscles while causing a significant decrease in iron levels in the brain, creating a negative correlation that exacerbates oxidative stress and insulin resistance in the hippocampus [11]. Group 4: Modern Lifestyle Concerns - The article notes that modern individuals sit for over eight hours daily, contributing to a surge in type 2 diabetes rates and a decrease in healthy life expectancy post-65 years [12]. - Insulin resistance from lack of exercise is linked to both physical and cognitive health deterioration, potentially triggering early onset of Alzheimer's disease [12]. Group 5: Recommendations for Physical Activity - The article suggests that exercise is essential for maintaining cognitive function, proposing simple methods to incorporate more movement into daily life, such as taking stairs, walking, and outdoor activities [16]. - It emphasizes that immediate action yields the greatest health benefits, particularly in middle age to prevent cognitive decline [16][14].

Core Viewpoint - Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with no effective treatment to reverse its progression, necessitating urgent action for better therapeutic options [2][3][6]. Group 1: Current State of Alzheimer's Disease - Over 50 million people globally suffer from Alzheimer's or related dementias, with projections indicating this number will double by 2050 [3]. - Annual global spending on Alzheimer's exceeds $1 trillion, making it one of the most costly health issues [3]. - The drug development landscape for Alzheimer's faces significant challenges, with a failure rate of 98% over recent decades [6]. Group 2: Research Findings - A recent study published in Cell identified two FDA-approved cancer drugs, letrozole and irinotecan, that, when used in combination, significantly improved memory and reduced Alzheimer's-related pathology in mouse models [4][17][20]. - The research utilized publicly available data to analyze gene expression changes in neurons and glial cells associated with Alzheimer's, leading to the identification of potential drug candidates [9][11][20]. - The study highlighted the importance of glial cell dysfunction alongside neuronal vulnerability in the disease's heterogeneous pathology [7][8]. Group 3: Methodology and Results - The research team compared gene expression features from Alzheimer's patients with a drug response database, narrowing down 1,300 drugs to 86, then to 10, and finally to 5 promising candidates [10][13]. - The combination therapy of letrozole and irinotecan was shown to reverse multiple Alzheimer's symptoms in mouse models, eliminating toxic protein plaques and restoring memory [17][20]. - The study emphasizes a cell-type directed, multi-target drug discovery strategy based on human data and real-world evidence, paving the way for precision medicine in Alzheimer's treatment [18][20].

Group 1 - The core message emphasizes the importance of early diagnosis and understanding of Alzheimer's disease, highlighting that many patients remain undiagnosed for an average of two years despite noticeable symptoms [4][8] - There is a common misconception that memory decline is a normal part of aging, which can lead to delays in seeking medical help [5][6] - Cognitive impairment is defined as a broader concept that includes mild cognitive impairment and dementia, aiming to raise awareness for early intervention [7][8] Group 2 - Not all cognitive impairments are Alzheimer's disease; various types of dementia exist, such as frontotemporal dementia and Lewy body dementia, which require different diagnostic approaches [21][19] - Diagnosis of Alzheimer's disease can be complex, as some patients may present atypical symptoms, necessitating comprehensive assessments and advanced imaging techniques like PET scans [22][29] - The article discusses the development of medications that can alleviate symptoms and improve the quality of life for Alzheimer's patients, although it cannot cure the disease [33][34] Group 3 - Caregivers of Alzheimer's patients face significant challenges and stress, often going unrecognized for their contributions and sacrifices [40][41] - The establishment of support groups and caregiver networks is crucial for providing emotional support and resources to those caring for Alzheimer's patients [49][50] - The article highlights the importance of community involvement and the expansion of caregiver support initiatives across various regions to enhance the well-being of both patients and caregivers [60][62]

Core Viewpoint - The National Health Commission of China has issued notifications prohibiting the use of two surgical procedures: "cervical deep lymphatic vessel/vein anastomosis" for Alzheimer's disease and "jejunum-ileum anastomosis" for type 2 diabetes treatment, due to concerns over their safety and efficacy [1][4][12]. Group 1: Alzheimer's Disease and Surgical Procedure - The "cervical deep lymphatic vessel/vein anastomosis" (LVA) is deemed to be in the early exploratory stage of clinical research, lacking clear indications and contraindications, as well as high-quality evidence supporting its safety and effectiveness [4][10]. - The procedure has been evaluated by experts, who concluded that its application in treating Alzheimer's disease is not supported by sufficient clinical evidence, and it poses potential risks that may outweigh benefits for patients with mild symptoms [9][10]. - The National Health Commission has mandated local health authorities to ensure that medical institutions cease the use of LVA for Alzheimer's treatment and to provide follow-up services for affected patients [11]. Group 2: Type 2 Diabetes and Surgical Procedure - The "jejunum-ileum anastomosis" has been evaluated and found to have uncertain safety and effectiveness for treating type 2 diabetes, with potential severe complications such as liver failure and malnutrition [12][14]. - Although some studies suggest that this procedure may improve blood sugar levels post-surgery, the overall clinical evidence remains limited, and it has not been included in the latest diabetes treatment guidelines [13][14]. - The National Health Commission has instructed health authorities to monitor and regulate the clinical application of this procedure, ensuring that institutions stop its use for diabetes treatment and enhance public health education [14].