Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study.

BACKGROUND: Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. METHODS: Data on memory complaints and cognitive function were collected among 1840 Chinese participants (aged ≥55 years old) in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. RESULTS: A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment after 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.04-2.48) and cognitive decline (OR = 1.30, 95% CI: 1.01-1.68). Furthermore, this association was more significant in males (OR = 2.10, 95% CI: 1.04-4.24 for cognitive impairment and OR = 1.87, 95% CI: 1.20-2.99 for cognitive decline) and in higher education level (OR = 1.79, 95% CI: 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI: 1.02-1.91 for cognitive decline). CONCLUSIONS: Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.

Intraventricular infusion of clusterin ameliorated cognition and pathology in Tg6799 model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by the deposition of amyloid-ß (Aß) in brain parenchyma and cerebral blood vessels as cerebral amyloid angiopathy (CAA). Clusterin, a chaperon protein associated with Aß aggregation, toxicity and transport through blood-brain barrier, may play a key role in the development of AD. Recently, clusterin peptide D-[113-122] was shown to mimic clusterin's function and exerted therapeutic effect in atherosclerosis. In this study, we investigated whether this clusterin peptide also affected (Aß) deposition in AD transgenic mouse. RESULTS: Using a micropump, synthetic peptide 113-122 of clusterin protein (20 µg/200 µl) was infused into the lateral ventricle of 8-month 5 × FAD transgenic mouse model (Tg6799), for 2 weeks. Water-maze testing showed an improved cognitive function of the Tg6799 mice treated with clusterin. Immunocytochemistry and quantitative analysis revealed that intraventricular (icv) administration of clusterin peptide in Tg6799 mouse reduced Aß plaques as well the severity of cerebral amyloid angiopathy. Enzyme-linked immunosorbent assay demonstrated a decreased in the soluble levels of Aß (Aß40 and Aß42) in the brain. Western-blot revealed an increased level of LRP-2 after clusterin peptide treatment. CONCLUSION: These results suggest that icv infusion of clusterin peptide D-[113-122] offers a promising therapeutic approach to reduce Aß deposition as well as CAA. The LRP2-mediated clearance system might be involved in the mechanism of these effects.

The role of amyloid beta clearance in cerebral amyloid angiopathy: more potential therapeutic targets.

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid ß-protein (Aß) in the leptomeningeal and cortical blood vessels, which is an age-dependent risk factor for intracerebral hemorrhage (ICH), ischemic stroke and contributes to cerebrovascular dysfunction leading to cognitive impairment. However clinical prevention and treatment of the disease is very difficult because of its occult onset and severity of the symptoms. In recent years, many anti-amyloid ß immunotherapies have not demonstrated clinical efficacy in subjects with Alzheimer's disease (AD), and the failure may be due to the deposition of Aß in the cerebrovascular export pathway resulting in further damage to blood vessels and aggravating CAA. So decreased clearance of Aß in blood vessels plays a crucial role in the development of CAA and AD, and identification of the molecular pathways involved will provide new targets for treatment. In this review, we mainly describe the mechanisms of Aß clearance through vessels, especially in terms of some proteins and receptors involved in this process.

Multiple biomarkers response in maize (Zea mays L.) during exposure to copper.

Biomarkers in higher plants played an important role to estimate exposure effects of pollutants in soil ecosystem and have received increasing attention in recent years. The qualitative and quantitative modifications arising in amplified fragment length polymorphism (AFLP) profiles as a measure of DNA effects were compared with a number of parameters, namely, the root length, total soluble protein content in root tips, chlorophylls content and shoot size to select the most sensitive biomarker responding to copper stress in the range of 0-600 mg/kg. The changes occurring in AFLP profiles of root tips following Cu treatment included loss of normal bands and appearance of new bands and variation in band intensity in comparison to that of the normal seedlings. A reduction in root length was observed at the 200 mg/kg of copper, which was accompanied with a decrease in total soluble protein content. According to their sensitivity to the copper toxicity, the above indicator rank in the following order: AFLP profiles > total soluble protein content > root length > chlorophylls content > shoot. We concluded that the AFLP offered a useful alternative biomarker assay for the detection of genotoxic effects of environmental pollutants.