Highly toxic Aβ begets more Aβ

<正>Alzheimer’s disease (AD) is the most common form of dementia-the 7^th leading cause of death worldwide.At the tissue level,AD is characterized by the presence of extracellular amyloid plaques that are comprised primarily of the amyloid-βpeptide (Aβ),     

A.A疗法对缺血性脑血管病的疗效观察

颈内动脉系统的缺血性脑血管病是神经科常见病、多发病,且致残率高。近年来,由于CT的应用,在诊断方面已获得突破性进展,然而,寻求新的有效的治疗方法仍是临床亟待解决的重要课题。两年来,笔者采用自体动脉加压灌注于病灶侧颈内动脉的方法(因为是用动脉血流灌注于动脉故简称为A.A疗法)对10例颈内动脉系统缺血性脑血管病进行治疗。现初步总结如下。     

A cortical form of CADASIL with cerebral Aβ amyloidosis

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was diagnosed by genetic testing in a 53-year-old patient, 10 years before death. Following two strokes with partial recovery, he developed rapidly progressive cognitive decline 3 years before death. Neuropathology confirmed CADASIL. Characteristic arteriolar changes were associated with subcortical infarcts, and status cribrosus in basal ganglia and the cortico-subcortical junctions. Leukoencephalopathy was very mild. Severe arteriolar changes in the cerebral cortex and leptomeninges were associated with numerous intracortical microinfarcts. There was abundant Abeta deposition throughout the cerebral cortex, mainly as Aβ42 diffuse plaques, frequently periarteriolar. There was no cerebral amyloid angiopathy apart from rare Aβ40 deposits around Notch3-positive deposits. Amyloid plaques were rare. Tau pathology was minimal. Alzheimer disease associated with CADASIL has been described, but the few reported cases had abundant amyloid plaques, amyloid angiopathy, fibrillar plaques and neurofibrillary tangles. Aβ accumulation could result from abnormal Aβ synthesis or impaired elimination due to the arteriolar changes of CADASIL. We did not find Aβ deposits in our other CADASIL cases with milder cortical arteriolar changes. Additional genetic predisposing factors were not identified. This case suggests that besides the classical, purely subcortical form of CADASIL, a “cortical” form with numerous lacunar infarcts and Aβ deposition in the cerebral cortex may occur and may be difficult to differentiate clinically from Alzheimer disease.     

A novel approach for Aβ₁₋₄₀ quantification using immuno-PCR

Several lines of evidence suggest that aggregation of the amyloid β-peptide (Aβ) in the brain is a trigger of Alzheimer's disease (AD). Thus, quantification of Aβ in several different types of samples from brain is fundamental for understanding AD pathogenesis. For analysis of the low levels of Aβ present in microdissected neurons, a more sensitive system than the ELISAs used today would be helpful. Here, we report a novel immuno-PCR (IPCR) system in which the lowest quantitative level of Aβ???? is 2 attomol/μL. We use the novel IPCR to quantify the intracellular Aβ???? levels in pyramidal neurons microdissected from human brain. We show that the level of Aβ???? is around 10 attomol/neuron, and thus, only 3 neurons are needed for analysis.     

A．A疗法对缺血性脑血管病的疗效观察

颈内动脉系统的缺血性脑血管病是神经科常见病、多发病。且致残率高。近年来，由于CT的应用，在诊断方面已获得突破性进展，然而，寻求新的有效的治疗方法仍是临床亟待解决的重要课题。两年来，笔者采用自体动脉加压灌注于病灶侧颈内动脉的方法(因为是用动脉血流灌注于动脉故简称为A．A疗法)对10例颈内动脉系统缺血性脑血管病进行治疗。现初步总结如下。     

腺苷A2A受体拮抗剂改善帕金森病运动并发症

目的 探讨腺苷A2A受体拮抗剂8-(3-Chlorostyryl)caffeine(CSC)对左旋多巴诱发的运动并发症的行为学与细胞学影响.方法 通过6-羟基多巴(6-OHDA)立体定向注射至大鼠前脑内侧束建立帕金森病(PD)动物模型.模型成功大鼠接受每日2次左旋多巴甲酯(50 mg/kg加12.5mg/kg苄丝肼)腹腔注射,持续22 d.在第23天,运动并发症模型组大鼠(n=8)继续接受如上用药,用药组(n=8)在左旋多巴注射前注射腺苷A2A受体拮抗剂CSC,均用药至第29天.同时设假手术组(n=8)和PD对照组(n=8).评估旋转时间,并采用免疫组织化学法和蛋白印迹法观察和检测纹状体区腺苷A2A受体的表达情况.结果 左旋多巴长期用药诱发PD大鼠模型旋转反应时间缩短,同时模型组损伤侧纹状体区腺苷A2A受体的表达升高[阳性细胞指数(IOD),(11.55±2.75)×104>],较假手术组[IOD,(6.02±1.29)×10±]和PD组[IOD,(5.60±1.83)×10±]有统计学意义(F=33.31,P<0.05).CSC用药逆转了左旋多巴诱导的PD大鼠旋转时间的缩短,损伤侧纹状体区腺苷A2A受体的表达[IOD,(5.80±1.56)×104>]也下调至对照组和PD组水平.结论 腺苷A2A受体参与了左旋多巴诱发的运动并发症的发生,腺苷A2A受体拮抗剂可能是治疗PD运动并发症有前景的药物.     

Differential effects of age on human striatal adenosine A₁ and A(2A) receptors

The aim of this study was to investigate the effect of age on the distribution of adenosine A₁ receptors (A₁Rs) and adenosine A_2A receptors (A_2ARs) in the striatum of healthy subjects using PET imaging with 8‐dicyclopropylmethyl‐1‐[¹¹C]methyl‐3‐propylxanthine ([¹¹C]MPDX) and [7‐methyl‐¹¹C]‐(E)‐8‐(3,4,5‐trimethoxystyryl)‐1,3,7‐trimethylxanthine ([¹¹C]TMSX), respectively. We recruited 8 young (22.0 ± 1.7 years) and 10 elderly (65.4 ± 7.6 years) volunteers to undergo [¹¹C]MPDX PET scanning, and 11 young (22.7 ± 2.7 years) and six elderly (60.7 ± 8.5 years) volunteers to undergo [¹¹C]TMSX PET scanning. A dynamic series of decay‐corrected PET scans was performed for 60 min following injection of [¹¹C]MPDX or [¹¹C]TMSX. We calculated the binding potential (BP_ND) of [¹¹C]MPDX and distribution volume ratio (DVR) of [¹¹C]TMSX in the striatum. The BP_ND of [¹¹C]MPDX was significantly lower in elderly than in young subjects, both in the putamen and head of the caudate nucleus. The BP_ND was negatively correlated with age in both the putamen and the head of the caudate nucleus. However, no difference was found between the DVR of [¹¹C]TMSX in the striata of young and elderly subjects, nor was there a correlation between age and the DVR of [¹¹C]TMSX. The effect of age on the distribution of A₁Rs in the human striatum described herein is similar to previous reports of age‐related decreases in dopamine D₁ and D₂ receptors. Unlike A₁Rs, however, this study suggests that the distribution of A_2ARs does not change with age. Synapse 66:832–839, 2012. © 2012 Wiley Periodicals, Inc.     

阿尔茨海默病自身抗Aβ抗体对血浆Aβ水平的影响

目的通过比较有无自身抗Aβ抗体的阿尔茨海默病(AD)患者和年龄匹配的健康老年对照者(aNC)血浆Aβ水平之间差异,研究自身抗Aβ抗体对血浆Aβ水平的影响。方法113例AD患者和155例aNC的血浆对Tg2576小鼠大脑组织连续切片进行免疫染色,并进行组织淀粉样蛋白免疫反应(TAPIR)测定。随后,TAPIR阳性和阴性血浆分别与人工合成的Aβ40、Aβ42进行免疫沉降,免疫沉降物经过western blot检测分析其免疫特性。最后通过一种双抗体夹心的ELISA精确定量所有血浆的Aβ水平。结果(1)自身抗Aβ抗体无差异地频繁出现于AD患者(45．1%)和aNC中(41．3%)(P＞0．05),并在免疫沉降过程中表现出与Aβ40更强的亲和力。(2)两组TAPIR 和TAPIR-血浆的Aβ40和Aβ42水平比较均无显著性差异(P＞0．05)。结论自身抗Aβ抗体不足以影响血浆Aβ水平,人类抗Aβ抗体产生和作用机制可能有别于转基因AD动物模型。     

A case of kleptomania?

We report on a case of kleptomania with manifestation as deceptive ordering by catalogue. The patient is additionally suffering from severe agoraphobia.     

A类群人格障碍与精神病

阐述分裂型人格障碍、分裂性人格障碍、偏执型人格障碍与精神分裂症、偏执性精神障碍的区别。     

蛋白激酶A与物质依赖

综述蛋白激酶A基本结构与功能、成瘾物质对蛋白激酶A的影响以及蛋白激酶A对药物滥用行为学反应及与物质依赖的研究进展。     

A Right to Sexuality?

In discourses on the sexuality of people with learning disabilities, there is one voice that goes unheard: that of people with learning disabilities themselves. Hence the motivation for the study described here. The author went to ask people with learning disabilities to enquire about the way they perceive their relationships and their sexuality, what they think of these topics and what is important to them in this respect. There is one major constant in all this information: that the circumstances of people's lives shape their perceptions of sexuality and relationships. Many service facilities have too many structural and organisational problems to allow relationships between service users, let alone value them. Professionals should be creative in finding ways to minimise the structural pressures exerted by the service facilities on the personal needs and wishes of people with learning disabilities.     

阿尔茨海默病中的Aβ研究进展

近年来由于分子生物学技术的应用推动了AD的病因研究 ,发现了几个AD的相关基因 ,其中最重要的是APP基因 ,由于APP蛋白断裂后产生具有毒性作用的Aβ。目前有许多研究者认为Aβ是AD的发病直接原因 ,本文就AD中的Aβ研究进展作一简要综述。