调心方对Aβ所致Alzheimer痴呆大鼠线粒体呼吸功能的影响

目的 观察调心方对 Aβ所致痴呆大鼠空间学习记忆能力和脑线粒体呼吸功能的影响。方法 大鼠左侧脑室注射 Aβ1 - 4 0活性片段造成大鼠 Aβ沉积型 Alzheimer病 (AD)模型 ,Morris水迷宫法观察大鼠空间学习记忆能力 ;Clark氧电极法测定各组大鼠皮层细胞线粒体呼吸功能和呼吸链氧化酶的活性以及调心方的作用。结果 与正常对照组比较 ,模型鼠空间学习记忆能力、皮层细胞线粒体呼吸功能和呼吸链中氧化酶活性均显著降低 ,调心方对上述指标有不同程度的改善作用。结论 调心方具有改善 AD大鼠空间学习记忆能力。

理脾阴正方提高Alzheimer痴呆小鼠抗氧化酶活性的研究

目的 :观察理脾阴正方提高机体抗氧化酶活性的作用。方法 :对老龄小白鼠用饮食不节、劳倦过度及皮下注射东莨菪碱等因素塑造脾虚Alzheimer痴呆模型 ,并用温补脾阳方药与理脾阴正方进行对比治疗 ,观察其对抗氧化酶活性的影响。结果 :东莨菪碱能降低超氧化物歧化酶、谷胱甘肽还原酶和单胺氧化酶的活性 ,而补益脾胃方药能明显提高上述三种酶的活性。结论 :理脾阴正方能显著提高东莨菪碱Alzheimer痴呆模型小鼠的抗氧化酶活性 ,降低过氧化损伤。

一种Alzheimer痴呆小鼠模型的建立

目的建立Alzheimer痴呆(Alzheimer dementia,AD)小鼠模型。方法 C57BL/6小鼠基底巨细胞核(NBM)注射Ibotenic酸制成AD模型。8周后应用8方向迷宫评价小鼠痴呆程度,应用免疫组织化学染色观察NBM和脑皮质胆碱能系统和β-淀粉样蛋白表达改变。结果 NBM内胆碱能神经元明显减少,5-羟色胺(5-HT)神经元和GABA神经元轻度减少。同侧额、顶叶皮质内胆碱能神经纤维显著减少,5-HT神经轴突轻度减少,伴大量β-淀粉样蛋白表达,GABA神经元则无明显变化。NBM毁损小鼠的工作记忆错误显著升高,小鼠的近事记忆明显损害。结论 NBM注射Ibotenic酸能建立一种可靠的AD小鼠模型。

Alzheimer痴呆的中医病因病机探析——Alzheimer痴呆的中医证型研究之一

应用国际通用的诊断标准选择１３９例Ａｌｚｈｅｉｍｅｒ痴呆病人，根据脏腑辨证、八纲辫证和病因辨证，全面系统地分析了Ａｌｚｈｅｉｍｅｒ痴呆的发病与五脏、气血阴精和痰瘀火邪关系。结果证明Ａｌｚｈｅｉｍｅｒ痴呆的发病与脏腑功能的失调，气血阴精的不足关系十分密切。其中心肾不足、气虚血亏、阴损精衰是发病的核心，与肝脾两脏也有一定的关系，而痰瘀火邪的作用则是Ａｌｚｈｅｉｍｅｒ痴呆发病的重要因素。

理脾阴正方提高Alzheimer痴呆模型动物学习记忆能力的机理探讨

观察理脾阴正方提高动物学习记忆能力的作用。用复合因素塑造老龄小鼠脾虚证模型 ,用东莨菪碱塑造Alzheimer痴呆模型 ,并分别用滋补脾阴和温补脾阳方药进行预防治疗。结果 ,脾虚及痴呆动物均出现水迷宫实验错误率增多 ,脑组织丙二醛 (MDA)含量增多 ,血液超氧化物歧化酶 (SOD)活性下降。补脾方药均能显著改善上述指标。脑脂质过氧化反应增强是Alzheimer痴呆的病理反应之一 ,包括过氧化物增多及抗氧化酶活性降低。脾虚证可加重这种病理反应 ,成为痴呆的起动因素之一。补脾方药通过降低过氧化损伤 。

安理申治疗Alzheimer痴呆的临床疗效观察

目的 评价安理申对Alzheimer病(AD)痴呆的临床疗效及其安全性。方法 AD患者20例,安理申5mg/日,每晚一次单剂量治疗,持续12周,自身对照。治疗开始、6周、12周分别进行简易智能状态检查(MMSE)、临床痴呆评定量表(CDR)、日常活动能力量表(ADL)和有关实验室检查。结果 18例患者完成观察,治疗6周后MMSE和ADL评分较治疗前明显改善(P<0.05),并维持至实验结束。治疗12周后,CDR总体功能评定明显改善(P<0.05)。实验室检查无肝肾功能等异常。结论 安理申是目前治疗老年性痴呆比较安全有效的一种药物。

Humanin蛋白在Alzheimer’s病模型中神经保护作用的研究进展

研究表明,Humanin蛋白通过多种方式在抗Alzheimer’s病的过程中发挥神经保护作用。本综述从Humanin的发现、结构特征、神经保护的机制及其新型同源分泌肽Rattin的结构与功能方面介绍Humanin蛋白在Alzheimer’s病中神经保护作用的最新研究进展。

肠道菌群与Alzheimer’s病的研究进展

Alzheimer’s病(AD)是好发于老年人的CNS退行性疾病,以认知能力下降及记忆受损为特征,同时伴发精神症状,严重影响患者的日常生活。肠道菌群是居住在胃肠道中的所有微生物的集合,是人体不可分割的一部分。肠道菌群可以通过脑-肠轴影响CNS,从而增加AD的发生风险。目前获批用于治疗AD的传统药物治疗效果不理想,因此急需一种新的AD治疗方法。本文将对肠道菌群与AD的关系进行阐述,探寻以肠道菌群为靶点的AD新疗法。

Autolysosomal acidification impairment as a mediator for TNFR1 induced neuronal necroptosis in Alzheimer’s disease

Neuronal necroptosis-an emerging form of regulated cell death associated with neuroinflammatory signaling:Alzheimer’s disease(AD)is characterized by the presence of extracellular amyloid-β(Aβ)plaques and intracellular tau neurofibrillary tangles as well as progressive neuronal loss.Recent evidence has suggested that prolonged neuroinflammation with increased levels of cytokines,arising from neuronal injury,innate immune responses from glial cells,and peripheral inflammation,leads to neuronal death and AD progression.

p38-MAPK and CDK5,signaling pathways in neuroinflammation:a potential therapeutic intervention in Alzheimer's disease?

Alzheimer’s disease(AD),the most common type of dementia,affects millions of people worldwide,putting a significant strain on healthcare infrastructure and societal resources.AD is characte rized by the build-up of amyloid-beta(Aβ)plaques and neurofibrillary to ngles containing hyperphosphorylated tau protein.

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Are we close to using Alzheimer blood biomarkers in clinical practice?

Alzheimer's disease(AD) is a progressive neurodegenerative disease histologically characterized by the presence of extraneuronal plaques,mainly formed by the 42-aminoacid isoform of amyloid-(Aβ_(1-42)),and by intraneuronal neurofibrillary to ngles,mainly formed by the tau protein and its hyperphosphorylated isoforms(p-tau).AD is the most common cause of dementia,with an estimated lifetime risk of about 1 in 10 for men and 1 in 5 for women.

Medin synergized with vascular amyloid-beta deposits accelerates cognitive decline in Alzheimer's disease:a potential biomarker

Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.

Microglial autophagy in neurogenesis:a new player in Alzheimer's disease

While extensive studies have illuminated the impact of Alzheimer's disease(AD) on neuronal survival,there is growing evidence that abnormal postnatal neurogenesis in early AD brains contributes to disease progression.Postnatal neurogenesis serves as a mechanism to replace dead or damaged neurons.New neurons generated from neural stem cells(NSCs) in the subgranular zone(SGZ) of the dentate gyrus integrate into the existing hippocampal circuit.

Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

Introduction:TAU isoforms as disease mediators:The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological conditions.In Alzheimer’s disease(AD)and related tauopathies,TAU also mislocalizes("TAU missorting")to the soma and the dendrites,where it eventually forms aggregates,the so-called neurofibrillary tangles(for review see Zimmer-Bensch and Zempel,2021;Zempel,2023).

小脑经颅磁刺激技术在Alzheimer’s病认知康复中的研究进展

Alzheimer’s病(AD)是以进行性认知功能障碍和行为损害为主要表现的神经退行性疾病,至今仍缺乏有效的药物治疗手段。经颅磁刺激(TMS)是一种非侵入性脑刺激技术,在改善和调节认知功能方面的作用日益凸显。以往TMS刺激的靶区集中在大脑皮质,但越来越多的研究表明,刺激小脑不仅可以调节大脑运动皮质区,并且对远隔的大脑认知相关脑区有调控和整合作用。因此,小脑已逐渐成为AD认知康复的非侵入性调控治疗潜在靶点。本文总结了小脑参与认知功能调控的解剖和功能基础以及小脑TMS调控认知功能的相关研究进展。

Neural stem cells promote neuroplasticity: a promising therapeutic strategy for the treatment of Alzheimer’s disease

Recent studies have demonstrated that neuroplasticity,such as synaptic plasticity and neurogenesis,exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease.Hence,promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated.Due to their significant ability to self-renew,differentiate,and migrate,neural stem cells play an essential role in reversing synaptic and neuronal damage,reducing the pathology of Alzheimer’s disease,including amyloid-β,tau protein,and neuroinflammation,and secreting neurotrophic factors and growth factors that are related to plasticity.These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain.Consequently,neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases.In this review,we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.