A new model for the pathophysiology of Alzheimer's disease: Aluminium toxicity is exacerbated by hydrogen peroxide and attenuated by an amyloid protein fragment and melatonin

Objectives. Although Alzheimer's disease (AD) is the leading cause of dementia in developed countries, there is an as yet unexplained lower prevalence of the disease in parts of Africa. AD is characterised by a catastrophic loss of neurons; free radicals (oxidative toxins) have been implicated in the destruction of the cells through the process of lipid peroxidative damage of cell membranes. Previously aluminium (Al) and a fragment of beta amyloid (Aβ 25 - 35) were shown to exacerbate tree-radical damage, while melatonin reduced this effect. The aim of the present study was: (i) to investigate the conditions detennining the toxicity of Al and Aβ 25 - 35; and (ii) to assess whether melatonin could attenuate the damage done by both aluminium and the amyloid fragment, thus suggesting a pathway for the aetiology of AD.Design. An in vitro model system was used in which free radicals were generated, causing lipid peroxidation of platelet membranes, thus simulating the disease process found in the brain.Results. 1. Al and Aβ 25 - 35 caused lipid peroxidation in the presence of the iron (II) ion (Fe2+, Al being more toxic than Aβ 25 - 35. 2. Aβ 25 - 35 attenuated the lipid peroxidation promoted by Al. 3. Hydrogen peroxide (H2O2 greatly exacerbated the toxicity of Al and Aβ 25 - 35. 4. Melatonin prevented lipid peroxidation by Al and Aβ 25 - 35 in the absence of H2O2, but only reduced the process when H2O2 was present.Conclusions. In the light of the results obtained from the present study, the following hypotheses are formulated. 1. In AD, excessive quantities of Al are taken up into the  brain, where the Al exacerbates iron-induced lipid peroxidatian in the Iysosomes. 2. In response, the normal synthetic pathway of amyloid protein is altered to produce Aβ fragments which attenuate the toxicity of Al. In the process of sequestering the Al and iron, immature plaques are formed in the brain. 3. Microglia are activated, in an attempt to destroy the plaques by secreting reactive oxygen species such as H2O2. At this point in the disease process, lipid peroxidation causes a catastrophic loss of brain cells. 4. Melatonin, together with other free radical scavengers in the brain, reduces the free-radical damage caused by Al and Aβ, except in the latter stages of the disease process. Since melatonin is produced by the pineal gland only in the dark, the excess of electric light in developed countries may help explain why AD is more prevalent in these countries than in rural Africa

Ebb and Flow When Navigating Adolescence: Predictors of Daily Hassles Among African-American Adolescent Girls

To examine the nature of daily hassles as perceived by African-American adolescen females. DESIGN AND METHODS . As part of a larger, cross-sectional study, nonrandom network sampling technique was used to survey 178 adolescent girls between the ages of 11 and 19. RESULTS . This study found that the most common hassles were school and academic, followed by family and economic hassles, peer and social hassles, and personal safety hassles. Socioeconomic factors were strongly associated with the level of hassles reported. PRACTICE IMPLICATIONS . Assess African-American girl's perception of daily hassles, specifically school- and family- related hassles, and also examine the interrelationship between the type of hassles and health problems.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71923/1/j.1744-6155.2002.tb00170.x.pd