整理 | GLP1减重宝典内容团队 诺和诺德预计将在下月初发布的研究结果可能为GLP-1药物——目前被数百万患者用于治疗糖尿病和减重——是否能减缓阿尔茨海默 病的进展提供最强的指示。 这两项试验，诺和诺德称其为"彩票"，正在测试其糖尿病药物Rybelsus ，该药物与Ozempic和Wegovy含 有相同的活性成分——司美格鲁肽——在数千名轻度阿尔茨海默病患者中，目标是将患者的认知衰退速度至少降低20%。 阿尔茨海默病专家表示，如果试验成功，这将为缓解这种定义为大脑中毒性淀粉样斑块的病症提供一种新的、方便的治疗方法，而全 球约有5000万人受此疾病影响。无论结果如何，研究人员预计将为未来研究提供重要线索，了解像司美格鲁肽这样的药物，以及礼来 的替尔泊肽和Mounjaro，如何在对抗阿尔茨海默病中发挥作用。 点击关注，追踪最新GLP-1资讯 阿尔茨海默病协会首席科学官Maria Carrillo表示，这项研究"有可能具有变革性。"然而，专家们一致认为，GLP-1类药物如何影响大 脑仍不清楚。进入试验的证据大多支持GLP-1类药物用于治疗与糖尿病和肥胖相关的痴呆症患者。2021年启动的阿尔茨海默病研究基 于动物研 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 2025 年 11 月 4 日， Nature 头条报道了一项研究成果—— 只需每天走上几千步，阿尔茨海默病的病情 发展就会减缓。 这项研究来自 麻总百瀚 （ Mass General Brigham ） / 哈佛医学院，于 2025 年 11 月 3 日在线发表于 国际顶尖医学期刊 Nature Medicine ，论文题为： Physical activity as a modifiable risk factor in preclinical Alzheimer's disease 。 该研究对 认知功能未受损的老年人进行了 14 年的追踪，发现 每天步行超过 5000 步或可降低阿尔茨海默 病临床前期的 tau 蛋白积累和认知衰退 。这是首批探索不同运动强度和阿尔茨海默病关键生物标志物间关 系的研究之一，并且提出了对老年人而言较易实现的运动目标，以减缓疾病进展。 在这项最新研究中，研究团队对参与哈佛衰老大脑研究 （Harvard Aging Brain Study） 项目的 296 名老 年人 （50-90 岁） 进行了定期检查，该项目旨在探究阿尔茨海默病的早期 ...

国际最新健康研究：日行5000步或助减缓阿尔茨海默病相关衰退 中新网北京11月4日电 (记者 孙自法)施普林格·自然旗下专业学术期刊《自然-医学》最新发表一篇健康 研究论文称，研究人员通过对认知功能未受损的老年人进行14年的追踪发现，每日步行超过5000步或可 降低阿尔茨海默病临床前期的tau蛋白积累和认知衰退。 这是首批探索不同运动强度和阿尔茨海默病关键生物标志物间关系的研究之一，并且提出了对老年人而 言较易实现的运动目标，以减缓疾病进展。 该论文介绍，缺乏运动是阿尔茨海默病的已知风险因素，亟需安全有效的方式来延缓疾病进展。动物研 究表明，锻炼可降低阿尔茨海默病相关病理变化，但运动对该疾病人类生物标志物的影响及其剂量-反 应关系尚不明确。迄今鲜少有研究使用活动的客观量表来检测其对淀粉样斑块和tau蛋白(阿尔茨海默病 的生物标志物)的作用，也无长期时间框架下的追踪研究。 在本项研究中，美国医疗机构麻总百瀚(MGB)团队和合作者一起，分析了哈佛老化大脑研究中294名认 知功能未受损的老年人(50-90岁)的数据，包括计步器记录的运动量、纵向淀粉样蛋白和tau蛋白的PET成 像数据，以及最长达14年的认知评估，发 ...

Core Insights - The study highlights the role of lipid metabolism dysregulation in promoting chronic microglial activation and neuroinflammation in Alzheimer's disease (AD) [2][6] - MFE-2 is identified as a potential drug target, with the small molecule CKBA showing promise in restoring MFE-2 expression and treating AD [6] Group 1: Research Findings - The expression level of MFE-2, a key enzyme regulating fatty acid β-oxidation, is found to be decreased in microglia from both human AD patients and AD model mice [3] - Specific knockout of MFE-2 in microglia of AD model mice leads to microglial abnormalities, neuroinflammation, and β-amyloid (Aβ) deposition [3] - The absence of MFE-2 promotes lipid accumulation, resulting in excessive arachidonic acid, increased mitochondrial reactive oxygen species (ROS), and production of pro-inflammatory cytokines [3] Group 2: Therapeutic Potential - The natural triterpenoid compound AKBA's derivative CKBA can bind with high affinity to MFE-2, stabilizing its levels and inhibiting excessive microglial activation [3] - CKBA improves neuroinflammation and pathological damage associated with Alzheimer's disease [3][6]

Core Insights - The article narrates the emotional journey of a caregiver, Zhu Maomao, who reflects on her experiences caring for her mother suffering from bipolar disorder and Alzheimer's disease, highlighting the complexities of their relationship and the impact of illness on family dynamics [1][2][4][5][7][19]. Group 1: Caregiver Experience - Zhu Maomao describes her role as a full-time mother and caregiver, emphasizing the challenges faced while raising her daughter, who has autism, alongside her mother's mental health struggles [4][5]. - The narrative reveals the emotional toll of caregiving, including feelings of helplessness and the transformation of the mother-daughter relationship as they navigate illness together [7][19]. - Zhu Maomao's reflections on her mother's decline illustrate the gradual loss of independence and the caregiver's evolving role, leading to a reversal of traditional family roles [19][20]. Group 2: Mother's Illness Journey - The article details the progression of the mother's bipolar disorder and subsequent diagnosis of early-onset Alzheimer's disease, including specific symptoms and changes in behavior over time [10][11][15]. - It highlights the mother's emotional resilience and moments of clarity amidst her illness, showcasing her attempts to maintain a connection with her family, particularly her granddaughter [5][15][25]. - The narrative also discusses the impact of medication on the mother's health and quality of life, including side effects and the challenges of managing her care [14][20]. Group 3: Family Dynamics - The relationship between Zhu Maomao and her mother is characterized by a blend of love, frustration, and a search for understanding, as they both cope with their respective mental health issues [31][32]. - The article touches on the societal perceptions of success and failure, contrasting the mother's life experiences with conventional standards, ultimately recognizing her wisdom and resilience as invaluable [31][32]. - The story concludes with reflections on loss and the complexities of familial love, emphasizing the importance of understanding and appreciating the sacrifices made by caregivers [34][35].

Core Insights - A study published in the Proceedings of the National Academy of Sciences reveals that during aging, men's brains exhibit more significant volume reduction and a faster atrophy rate compared to women [1] Group 1: Research Findings - The research team from the University of Oslo analyzed MRI brain scans from 4,726 healthy participants, totaling 12,500 scans, with each participant undergoing more than two scans over intervals of three years [1] - Men showed a notable volume decrease in various brain regions, such as the postcentral cortex, which is responsible for processing touch, pain, temperature, and body posture, with an annual atrophy rate of approximately 2.0% for men compared to 1.2% for women [1] - The findings suggest that men age faster and have a shorter average life expectancy [1] Group 2: Implications for Neurodegenerative Diseases - Understanding the natural aging process of a healthy brain can enhance the comprehension of the development mechanisms of neurodegenerative diseases [1] - If Alzheimer's disease is related to these changes, faster atrophy should be observable in critical areas of the female brain, such as the hippocampus and precuneus, but the study did not find such phenomena [1] - The complexity of Alzheimer's disease etiology indicates that age-related brain atrophy alone is insufficient to reveal its mechanisms [1] Group 3: Gender Differences in Alzheimer's Disease - The results imply that the higher incidence of Alzheimer's disease in women may be linked to differences in lifespan or disease susceptibility rather than brain volume changes [1] - After adjusting for education levels, the atrophy rate in certain male brain regions was no longer significantly faster than in females [1] - When comparing men and women with the same life expectancy (rather than age), the rate of brain decline was found to be similar between the two groups [1]

Core Insights - A research team led by Huang Lusheng from Jiangxi Agricultural University has revealed a new mechanism mediating synaptic damage in cognitive impairment dogs, focusing on the interaction between microglial cells C1QA and neurons CRT [1][3] - The study published in the journal "National Science Review" highlights the increasing prevalence of Alzheimer's disease (AD), with over 55 million patients globally and approximately 9.83 million in China [1][3] Group 1 - The research innovatively uses dogs as a model to systematically explain the molecular mechanisms of aging and related cognitive impairments, enhancing the application of dogs as a translational model for human AD [3] - The team has provided a theoretical basis for early intervention in canine cognitive impairment by analyzing the differences in glial cells under physiological aging and pathological states of cognitive decline [3] - The findings may offer potential molecular biomarkers for the early diagnosis of dementia and provide important cellular mechanism references for understanding its pathogenesis [3]

Core Viewpoint - The research highlights that Alzheimer's disease (AD) is not solely characterized by the accumulation of amyloid-beta (Aβ) plaques and tau tangles, but also involves a disruption in communication between neurons and glial cells, particularly astrocytes and microglia, which is crucial for disease progression [2][3][5]. Group 1: Research Findings - The study published in Cell provides a comprehensive view of how brain cells interact in Alzheimer's patients, revealing that the disruption of information exchange between neurons and glial cells is closely related to the development of AD [3][5]. - A protein named AHNAK has been identified as a key driver protein in the disrupted protein networks associated with Alzheimer's disease, suggesting a new avenue for innovative treatment strategies [3][9]. - The research team conducted deep proteomic analysis on the parahippocampal gyrus (PHG) of 198 deceased Alzheimer's patients, mild cognitive impairment (MCI) patients, and normal controls to understand molecular dysregulation in AD [6][7]. Group 2: Key Protein Networks - The analysis revealed over 300 key driver proteins (KDPs) that play significant roles in triggering or accelerating Alzheimer's disease, with AHNAK being one of the most prominent proteins found in astrocytes [8][11]. - The study indicates that in Alzheimer's disease, the balance between neurons and glial cells is disrupted, leading to hyperactivity of glial cells and diminished neuronal function, which correlates with increased inflammation [8][11]. - Different biological factors, such as sex and genetic background, can influence the expression of these protein networks, with carriers of the APOE4 gene showing distinct patterns of protein network disruption compared to non-carriers [11].

Core Insights - The prevalence of Alzheimer's disease among individuals aged 60 and above in China exceeds 5%, and it reaches as high as 30% in those aged 85 and above [1] - Genetic factors play a significant role in Alzheimer's disease, with 5%-10% of cases being hereditary [1] - The presence of pathogenic genes such as APP, PS1, and PS2 indicates a high likelihood (over 95%) of developing Alzheimer's, often at an early age [1] - Risk genes like APOEε4 increase the probability of developing the disease but have a lower chance of being inherited [1] Genetic Testing and Early Detection - It is recommended for children of parents with Alzheimer's to undergo genetic testing to determine the presence of pathogenic or risk genes [2] - Early diagnosis through methods like PET scans and cerebrospinal fluid tests can help in timely intervention with antibody drugs to slow disease progression [2] Prevention Strategies - Prevention of Alzheimer's should begin early in life, emphasizing the importance of good learning habits and cognitive engagement from youth [2] - Building cognitive reserves throughout life is crucial for effectively preventing neurodegenerative diseases [2]

Core Insights - The article discusses the pervasive presence of nanoplastics/microplastics (NMP) in the environment and their potential health impacts on humans, particularly concerning cognitive decline and Alzheimer's disease [2][3][4]. Group 1: Health Impacts of Nanoplastics - Research from the University of Rhode Island indicates that polystyrene nanoplastics (PS-NMP) can accumulate in the brain and lead to cognitive decline, especially in individuals carrying the Alzheimer's risk gene APOE4 [4][5]. - The APOE4 gene significantly increases the risk of Alzheimer's disease, with a threefold increase in risk for one copy and an 8-12 fold increase for two copies [5]. - The study highlights that lifestyle and environmental factors, alongside genetic predisposition, play a crucial role in the development of Alzheimer's disease [5]. Group 2: Experimental Findings - The research involved genetically modified mice, one group carrying the APOE4 gene and another carrying the APOE3 gene, exposed to PS-NMP in drinking water for three weeks [6]. - Results showed that PS-NMP entered various organs, including the brain, and affected cognitive abilities, with APOE4 mice exhibiting altered behavior and impaired memory recognition [6][7]. - The study found gender-dependent behavioral changes in mice, mirroring observed differences in Alzheimer's patients, where male patients show more apathy and female patients exhibit greater memory decline [7]. Group 3: Broader Implications - The findings raise concerns about the cognitive decline associated with exposure to nanoplastics, which are common environmental toxins [8]. - A related study published in Nature Medicine confirmed the presence of microplastics in human brains, particularly in dementia patients, suggesting a link between microplastics and neurodegenerative diseases [12]. - Another study revealed that microplastics in the bloodstream could induce cerebral thrombosis, leading to neurobehavioral abnormalities [13].