Plasma renin–angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer's disease and show gender differences but are not related to apolipoprotein E genotype

Alterations in blood pressure and components of the renin–angiotensin system (RAS) contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. Aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase N (APN) and aminopeptidase B (APB) catabolise circulating angiotensins, whereas insulin-regulated aminopeptidase (IRAP) has been described as the AT₄ receptor. We have found in AD patients a significant decrease of APA activity in men but not in women, and of APN, APB and IRAP in both genders, when compared with control subjects. No changes were found in ASAP activity. Also, APN, APB and IRAP but not APA correlated with the Mini–Mental test, but no relationship with APOE genotype was found. We conclude that several components of the RAS are modified in AD patients, with gender differences. Furthermore, ROC analysis indicates that APN, APB and IRAP activities could be useful non-invasive biomarkers of AD from the earliest stages.     

THE DEVELOPMENT OF AN ELISA FOR CHICKEN APOLIPOPROTEIN II QUANTITATION

ABSTRACT

Polyclonal antibodies raised against chicken apoII was characterised for its use in Western blotting and ELISA detection systems of apoII in chicken plasma. The antibody has a high avidity and specificity for apolipoprotein II (apoII). Western blots show that the antibody reacts with a single band at 15 kDa. The antibody was used for setting up both direct and indirect ELISA assays for apoII. The indirect ELISA has a broader detection range (10–1600 U/mL) than the direct ELISA (10–100 U/mL). It was found that both ELISA systems discriminate very well between vitellogenic (laying hen) and non-vitellogenic (rooster) plasma. The indirect ELISA, due to its broad detection range, can potentially be used for monitoring female reproductive cycles, accidental and environmental exposure of males to estrogen, and for apoII secretion by cultured hepatocytes and hepatomas.     

Opportunities for an atherosclerosis vaccine: From mice to humans

Atherosclerosis, the major underlying cause of cardiovascular diseases (CVD), is the number one killer globally. The disease pathogenesis involves a complex interplay between metabolic and immune components. Although lipid-lowering drugs such as statins curb the risks associated with CVD, significant residual inflammatory risk remains. Substantial evidence from experimental models and clinical studies has established the role of inflammation and immune effector mechanisms in the pathogenesis of atherosclerosis. Several stages of the disease are affected by host-mediated antigen-specific adaptive immune responses that play either protective or proatherogenic roles. Therefore, strategies to boost an anti-atherogenic humoral and T regulatory cell response are emerging as preventative or therapeutic strategies to lowering inflammatory residual risks. Vaccination holds promise as an efficient, durable and relatively inexpensive approach to induce protective adaptive immunity in atherosclerotic patients. In this review, we discuss the status and opportunities for a human atherosclerosis vaccine. We describe (1) some of the immunomodulatory therapeutic interventions tested in atherosclerosis (2) the immune targets identified in pre-clinical and clinical investigations (3) immunization strategies evaluated in animal models (4) past and ongoing clinical trials to examine the safety and efficacy of human atherosclerosis vaccines and (5) strategies to improve and optimize vaccination in humans (antigen selection, formulation, dose and delivery).     

APOE and neuroenergetics: an emerging paradigm in Alzheimer's disease

APOE is the major known genetic risk factor for late-onset Alzheimer's disease. Though relationships between APOE-encoded apolipoprotein E and β-amyloid are increasingly well described, mounting evidence supports wide-ranging effects of APOE on the brain. Specifically, APOE appears to affect brain network activity and closely related neuroenergetic functions that might be involved in vulnerability to neurodegenerative pathophysiology. These effects highlight the salience of further investigation into the diverse influences of APOE. Therefore, this article reviews the interplay between APOE and neuroenergetics and proposes areas for further investigation. This research might lead to the identification of novel therapeutic targets for the treatment and/or prevention of Alzheimer's disease.     

Apolipoprotein E genotypes and neuropsychiatric symptoms and syndromes in late-onset Alzheimer's disease

Neuropsychiatric symptoms (NPS) in dementia, previously denominated as behavioural and psychological symptoms of dementia, are often more distressing, impairing, and costly than cognitive symptoms, representing a major health burden for older adults. These symptoms are common features of Alzheimer's disease (AD), and are one of the major risk factors for institutionalization. There is a high prevalence of neuropsychiatric disturbances in patients with AD, including depression, anxiety, apathy, psychosis, aggression, and agitation. At present, the role of the apolipoprotein E (APOE) genotypes in the development of NPS or neuropsychiatric syndromes/endophenotypes in AD patients is unclear. In this article, we summarized the findings of the studies of NPS and neuropsychiatric syndromes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between the APOE polymorphism and NPS in late-onset AD, other studies reported a significant association between the APOE ?4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. However, current cumulative evidence coming from the few existing longitudinal studies shows no association of APOE genotypes with NPS as a whole in AD. Some negative studies that focused on the distribution of APOE genotypes between AD patients with or without NPS further emphasized the importance of sub-grouping NPS in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, possible lack of statistical power to detect associations in the negative studies, and small sample sizes generating false positives that cannot be consistently replicated. Finally, many reviewed studies were cross-sectional, whereas it would be of paramount importance to evaluate the risk for incident NPS in relation to the APOE genotype in prospectively followed cohorts of AD patients. In fact, identifying predisposing genetic risk factors may allow us to understand the pathophysiological features of neuropsychiatric syndromes or symptoms in AD, so optimizing possible therapeutic options.     

Apolipoprotein E e4 and its prevalence in early childhood death due to sudden infant death syndrome or to recognised causes

BACKGROUND:: Specific genetic polymorphisms have been shown to be more common in unexplained infant death. The APOE genotype exhibits opposite effects at the extremes of age with protective effects of e4 on perinatal mortality but detrimental effects as age progresses. OBJECTIVE:: To determine whether the APOE e4 allele is associated with early childhood (1 week-2 years) unexplained death ('sudden infant death syndrome', SIDS) or with recognised causes (non-SIDS) and to compare these cohorts with published perinatal and adult data. METHODS:: DNA was extracted from spleen tissue of children dying in South East Scotland between 1990 and 2002. APOE alleles (e2, e3, e4) were determined using PCR. Comparisons of allele frequencies between groups were made. RESULTS:: There were 167 SIDS cases and 117 non-SIDS cases. Allele distributions of SIDS cases were similar to healthy newborns. Allele distributions of non-SIDS cases were more similar to adults than to healthy newborns. The percentage of children with at least one e4 allele was significantly lower in non-SIDS compared to SIDS (p=0.016). Non-SIDS cases had a higher frequency of e3 compared to SIDS cases (p=0.01) and to healthy newborns (0.005). CONCLUSIONS:: Children dying from identified causes have different APOE allele distributions from SIDS cases, but are similar to adults. Children dying from SIDS have an allele distribution comparable to healthy newborns. The prevalence of e4 in SIDS is not of an order to contribute significantly to the age-related decline in e4.     

人血浆载脂蛋白AⅠ的纯化

 目的  初探大规模纯化人血浆载脂蛋白AⅠ(apolipoprotein AⅠ,ApoAⅠ）的低成本生产工艺。方法  以人血浆组分Ⅳ为原料,通过等电点沉淀、阴离子层析、低温乙醇沉淀和超滤等步骤纯化ApoAⅠ蛋白,并放大实验室纯化方法来纯化ApoAⅠ。结果  放大的纯化方法生产的ApoAⅠ的得率和纯度分别为59.0%和85.6%,经相关方法验证为人血浆ApoAⅠ。结论  实验室方法放大的纯化工艺可纯化ApoAⅠ。     

脑梗死患者脉搏波速度与载脂蛋白、胆红素、尿酸的相关性

目的探讨脑梗死患者脉搏波速度与血脂、尿酸及胆红素的相关性。方法选择脑梗死组和健康对照组各30例,进行脉搏波速度、血脂、胆红素、尿酸的测定。结果脑梗死组脉搏波速度、尿酸明显高于对照组,胆红素明显低于对照组,差异有统计学意义（P〈0.05）。脑梗死组总胆固醇及甘油三酯、低密度脂蛋白均高于对照组,但差异没有明显统计学意义,脑梗死组的载脂蛋白B/载脂蛋白A大于对照组,差异有统计学意义。推断脑梗死患者脉搏波速度与载脂蛋白B/载脂蛋白A（ApoB/ApoA）及尿酸呈正相关,与间接胆红素呈负相关。结论脑梗死患者的脉搏波速度明显快于对照组,且与载脂蛋白、胆红素及尿酸均有相关性,脉搏波速度可作为脑梗死危险度的预测因子。