视觉分析18F-Florbetaben在认知功能正常中国人群脑内的分布特征

目的 探讨视觉分析β淀粉样蛋白（Aβ）示踪剂氟18-氟比他班（¹⁸F-FBB）在认知功能正常中国人群脑内的分布特征及安全性评价。 方法 前瞻性纳入经确诊的认知功能正常受试者31例,其中男14例,女17例,平均（65.0±7.69）岁,均进行¹⁸F-FBB PET/CT脑部显像。从31例中随机选取6例作为对照[男2例,女4例,平均（66.0±7.19）岁]于1周后再进行碳11-匹兹堡化合物（¹¹C-PIB）PET/CT脑部显像。视觉定性评估¹⁸F-FBB和¹¹C-PIB在脑内的分布特征,并观察所有受试者注射¹⁸F-FBB后的不良事件。 结果 ¹⁸F-FBB在脑内正常分布特征为白质明显非特异性摄取,其余脑区均未见放射性摄取。31例¹⁸F-FBB受试者中30例（96.8%）为PET阴性显像,1例（3.2%）PET阳性显像,示踪剂主要浓聚于眶上额叶及外侧颞叶;6例¹¹C-PIB对照受试者中5例（83%）为PET阴性显像,1例¹¹C-PIB及¹⁸F-FBB PET均为阳性显像;¹⁸F-FBB的白质放射性摄取明显高于¹¹C-PIB 。注射¹⁸F-FBB后受试者中未见明确与药物相关的严重不良反应。 结论 在认知功能正常中国人群中¹⁸F-FBB的分布特征与¹¹C-PIB相同;¹⁸F-FBB药物使用安全,可用于无创性评估脑内Aβ沉积。     

老年性痴呆发病机制的研究进展

老年性痴呆的发病机制十分复杂，包括早老素等遗传基因的突变、异常过度磷酸化的tau蛋白引起的细胞骨架改变、脑内乙酰胆碱含量减少等中枢神经系统递质代谢障碍、淀粉样前体蛋白代谢失调引起的细胞外老年斑的形成、细胞内钙代谢紊乱、免疫炎症反应、自由基损伤学说和神经细胞凋亡等发病机制，下面将对AD的各种发病机制进行一一综述。     

凝血四项和血脂检测对评估绝经后2型糖尿病患者血管病变的临床意义*

目的探讨女性绝经后2型糖尿病(T2DM)患者凝血功能和血脂水平的变化及其与血管并发症的关系。方法分别检测(T2DM)组(n=205)和对照组(n=105)血浆凝血酶原时间(PT)、活化部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)和甘油三酯(TG)。结果 (1)T2DM组与对照组比较,无血管病变者PT、APTT显著下降(t=2.139、1.982,P0.05),FIB显著上升(t=2.138,P0.05);伴血管病变组PT、APTT和TT均显著下降(t=8.554、6.263和4.852,P0.01),FIB水平显著上升(t=3.537,P0.01)。(2)T2DM组与对照组比较,无血管病变和伴血管病变组TG、TC和LDL-C均显著升高(t=2.226、2.096和2.223,P0.05;t=4.940、3.055和3.106,P0.01),T2DM组组内比较,6.256,P0.05)。结论分析凝血四项和血脂水平对把握病情、诊断血管病变、指导治疗及预防糖尿病并发症有重要意义,故应尽早实施监测。     

Reversible Periventricular Hyperintensity Lesions in Cerebral Amyloid Angiopathy: A Case Mimicking Cerebral Amyloid Angiopathy-related Inflammation

A 59-year-old man with progressive cognitive decline and mood disturbances was admitted to the hospital. Brain magnetic resonance imaging revealed marked white matter hyperintensity (WMH) and widespread lobar cerebral microbleeds. Because he had untreated hypertension, we started antihypertensive treatment and found a significantly improved cognitive function and WMH regression. We diagnosed him with cerebral amyloid angiopathy (CAA) based on the modified Boston Criteria with the rare apolipoprotein E (ApoE) ε2/ε4 genotype. The mechanism underlying reversible leukoencephalopathy in CAA may be related to the loss of autoregulation of brain circulation: cerebrovascular amyloid β deposits damaged the blood-brain barrier of the capillaries, which led to vasogenic edema induced by blood pressure surges.     

Amyloid deposits in aortic and mitral valves

Summary The material from 100 consecutive aortic and mitral valve operations has been studied histologically with particular reference to the presence of amyloid deposits. Sixty seven per cent were positive (aortic 88%, mitral 45%).The simultaneous occurrence of calcification of the valves and amyloid degeneration as well as of calcification and hyalinization was significant. Similarly there was significantly more amyloid in the older age groups, as well as a significant correlation between the degree of hyalinization of the valve and amyloid.]Thirty-two patients had previously suffered from rheumatic fever. The heart valves of these patients did not differ histologically from the others, whereas significantly more amyloid was observed in the stenotic mitral valves than in the mitral valves which were insufficient.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。     

Intracellular pH regulates amyloid precursor protein intracellular domain accumulation

The amyloid precursor protein (APP) metabolism is central to pathogenesis of Alzheimer's disease (AD). Parenchymal amyloid deposits, a neuropathological hallmark of AD, are composed of amyloid-beta peptides (Abeta). Abeta derives from the amyloid precursor protein (APP) by sequential cleavages by beta- and gamma-secretases. Gamma-secretase cleavage releases the APP intracellular domain (AICD), suggested to mediate a nuclear signaling. Physiologically, AICD is seldom detected and thus supposed to be rapidly degraded. The mechanisms responsible of its degradation remain unknown. We used a pharmacological approach and showed that several alkalizing drugs induce the accumulation of AICD in neuroblastoma SY5Y cell lines stably expressing APP constructs. Moreover, alkalizing drugs induce AICD accumulation in naive SY5Y, HEK and COS cells. This accumulation is not mediated by the proteasome or metallopeptidases and is not the result of an increased gamma-secretase activity since the gamma-secretase cleavage of Notch1 and N-Cadherin is not affected by alkalizing drug treatments. Altogether, our data demonstrate for the first time that alkalizing drugs induce the accumulation of AICD, a mechanism likely mediated by the endosome/lysosome pathway.     

MiRNA-132上调脑源性神经营养因子表达抑制β-淀粉样蛋白诱导的神经元损伤研究

研究背景脑源性神经营养因子(BDNF)在阿尔茨海默病(AD)发病机制中发挥重要作用,微小RNA-132(mi RNA-132)在神经元呈高表达,可以通过调控靶基因表达参与BDNF介导的神经发育过程。本研究旨在探讨阿尔茨海默病神经元模型中mi RNA-132与BDNF的调控关系和神经保护作用。方法体外培养海马神经元72 h后慢病毒转染mi RNA-132,并于体外培养第7天以β-淀粉样蛋白(Aβ)处理制备阿尔茨海默病神经元模型;实时荧光定量聚合酶链反应观察对照组与AD组mi RNA-132表达差异以及不同处理组BDNF m RNA表达变化,噻唑蓝法观察不同处理方式对细胞活性的影响。结果 (1)AD组海马神经元mi RNA-132(t=13.888,P=0.000)和BDNF m RNA(t=-12.274,P=0.000)表达水平均低于对照组。(2)原代培养的海马神经元经慢病毒转染后倒置相差荧光显微镜可见绿色荧光蛋白,对照组(t=16.135,P=0.000)和AD组(t=8.656,P=0.000)转染过表达mi RNA-132后均能上调BDNFm RNA表达。(3)AD组海马神经元活性降低(t=-6.023,P=0.000),AD组转染mi RNA-132后神经元活性增强(t=3.385,P=0.007),予以外源性BDNF共培养后神经元活性明显改善(t=3.672,P=0.004)。结论阿尔茨海默病神经元模型mi RNA-132和BDNF表达水平均下降,mi RNA-132可上调BDNF表达,提示mi RNA-132和BDNF对阿尔茨海默病神经元模型具有神经保护作用,有望为阿尔茨海默病诊断与治疗提供新的视角。     

Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex

Summary This report presents a variant of Gerstmann-Sträussler syndrome (GSS). A 53-year-old female had developed slowly progressive dementia and atactic gait since the age of 45. No myoclonic jerks and periodic synchronous discharges were observed throughout the illness. The neuropathological study revealed that many amyloid plaques and widespread Alzheimer's neurofibrillary tangles (NFTs) appeared in the cerebral cortex. Characteristically, the plaques reacted with anti-prion protein and none of them reacted with anti- protein, and they were made of many components, including amyloid cores, macrophages laden with lipid granules and/or degenerated neurites. Neuropil threads were seen mainly in amyloid plaques. Moreover, plaques appeared which were confluent and laminar in arrangement in the fifth and sixth cortical layers and had a close relationship to the neuronal loss. There was no spongiform change in the cerebral cortex or cerebellum. The cerebellum was almost intact except for a few amyloid plaques. Ultrastructurally, some of the plaques simulated kuru plaques and others had many degenerated neurites possessing paired helical filaments and other accumulated organelles. GSS has been proposed to include cases with progressive ataxia, dementia and massive multifocal plaques in the brain with or without cerebral spongiform changes. The case presented here is a very peculiar case of GSS. Recently, similar cases have been reported in some large families, diagnosed as familial Alzheimer's disease. These cases may be a telencephalic form with numerous NFTs of GSS.     

Contributors to white matter damage in the frontal lobe in Alzheimer's disease

Abnormalities of cerebral white matter are present in a majority of patients with Alzheimer's disease (AD) and probably contribute to motor dysfunction and cognitive impairment. The white matter abnormalities are usually attributed to degenerative vascular disease and cerebral amyloid angiopathy (CAA) but the evidence is scanty or inconclusive. In the present study we examined sections of frontal lobe from 125 autopsy-confirmed cases of AD and assessed the relationship of degenerative large and small vessel disease, CAA, parenchymal Abeta load and APOE genotype, to several objective measures of white matter damage: extent of immunolabelling for glial fibrillary acidic protein (GFAP), axonal accumulation of amyloid precursor protein (APP), axon density in superficial and deep white matter, and intensity of staining for myelin. We found no association between atherosclerosis, arteriolosclerosis, CAA or APOE genotype and white matter damage. However, labelling of white matter for GFAP correlated strongly with the parenchymal Abeta load (P = 0.0003) and with APP accumulation (P = 0.008). Our findings suggest that severity of frontal white matter damage in AD is closely related to parenchymal Abeta load and that in most cases the contribution of degenerative vascular disease, CAA and APOE is relatively minor.