Ceruloplasmin and iron in Alzheimer's disease and Parkinson's disease: a synopsis of recent studies.

Ceruloplasmin (Cp) concentration and oxidative activity in serum are lowered in Parkinson's disease (PD). In most PD patients, iron increases in the substantia nigra in the midbrain. In PD, the low Cp concentration and activity in serum and the high iron amounts in the substantia nigra appears to be correlated. An hereditary background is common in PD and variations in the Cp gene that have been found in PD are associated with high iron levels in the substantia nigra. Variations in Cp synthesis and in the incorporation of copper into the Cp molecule are essential features of PD. In Alzheimer's disease (AD), the Cp activity in serum is lowered but not the concentration, except in the advanced stages of the disease. Generally, iron is not increased in the AD brain. In the AD brain, iron accumulates in neuritic plaques and in neurofibrillary tangles. There is also increased risk of iron-mediated tissue damage, which may possibly be counteracted by Cp. At the same time, the AD brain is short in copper, which presumably results in the deficient activity of many copper enzymes in the brain, in addition to Cp. Lowered Cp activity in serum most likely stems from lessened incorporation of copper in the Cp molecule and similar incorporation defects might also apply to other copper enzymes in AD.

Ceruloplasmin and iron proteins in the serum of patients with Alzheimer's disease.

BACKGROUNDS/AIMS: The oxidative activity of ceruloplasmin (CP) in serum has been found to be lowered in patients with Alzheimer's disease (AD). We investigated whether changes in CP were reflected by altered iron parameters in AD patients. METHODS: Iron parameters, and CP concentration, activity and specific activity were determined in the serum of 41 AD patients and controls. RESULTS: CP activity and specific activity were significantly lower in the AD patients. CP concentration and activity were negatively correlated with the ferritin concentration in both groups. CP concentration was positively correlated with age in the control group but not in the patients group. CONCLUSION: The lowered CP activity in the serum of AD patients was not reflected by the iron parameters. As CP concentration only rises with age in the controls, this may indicate failing adaption to age-related alterations in iron metabolism in AD patients.

Case-control studies on ceruloplasmin and superoxide dismutase (SOD1) in neurodegenerative diseases: a short review.

This short review describes a series of case-control studies on the concentration and oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Down's syndrome (DS). The same parameters were re-examined in the PD patients 5 years later. The specific oxidative activity (oxidative activity related to mass) of CP was calculated in PD and DS. In AD and PD the oxidative activity of CP and SOD1 activity was significantly lower in patients than controls. The specific oxidative activity of CP was also significantly lower in PD patients. The difference in all parameters determined was still present 5 years later in PD patients. There was no difference in the concentration or activity of CP in patients with DS and controls. Because of the gene-dose effect (the gene for SOD1 is located on chromosome 21); the SOD1 activity was 50% higher in the patients than the controls. The CP specific oxidative activity and SOD1 activity were found to be significantly lower in the older (>40 years) than the younger DS patients. Whether changes in CP and SOD1 in AD, PD and DS are primary changes or a result of prolonged disease burden needs to be examined.

The distribution of four trace elements (Fe, Mn, Cu, Zn) in forage and the relation to scrapie in Iceland.

BACKGROUND: Previous studies indicated that the iron (Fe)/manganese (Mn) ratio in forage of sheep was significantly higher on scrapie-afflicted farms than on farms in other scrapie categories. This study was conducted to examine whether Fe and Mn in forage of sheep varied in general according to the scrapie status of different areas in the country. Copper (Cu) and zinc (Zn) were also included because of a possible relation to scrapie. METHODS: The country was subdivided into seven Areas (I-VII). Three Areas (I, IV, VII) were designated scrapie-free (never diagnosed or eradicated) and three as scrapie-endemic (II, III, VI); status of Area V was taken as unsettled. Of the harvest 2007 1552 samples were analysed from 344 farms all over the country, mostly grass silage from plastic bales (>90%) and from the first cut (70% or more). Results were expressed as mg kg(-1) dry matter. RESULTS: Fe varied enormously from less than 100 mg kg(-1) to 5000 mg kg(-1). Mn varied nearly thirtyfold (17-470 mg kg(-1)). Fe concentration was significantly lower in Area I than in Areas II, V and VI. Mn concentration was significantly higher in Areas I, IV and VII than in Areas II, III, V and VI. The Fe/Mn ratio was significantly less in Area I than in the other areas (except Area IV). Mean Cu concentration was 6.6-8.3 mg kg(-1) and the mean Zn concentration was 24-29 mg kg(-1). They differed significantly in some areas. CONCLUSIONS: 1) Fe tended to be in lower amounts in sheep forage in scrapie-free than in endemic areas; 2) Mn was in higher amounts in forage in scrapie-free than endemic areas; 3) the Fe/Mn ratio was lower in scrapie-free than in endemic areas; 4) the Fe/Mn ratio may possibly be used as an indicator of scrapie status; 5) Cu and Zn in sheep forage were not related to scrapie; 6) further study on the role of Fe and Mn in the occurrence of scrapie in Iceland is needed.

Ceruloplasmin and superoxide dismutase (SOD1) in heterozygotes for Wilson disease: A case control study.

At the time of this study, there were five known patients with Wilson disease (WD) in Iceland. The mutation, a 7-bp deletion in exon 7 on chromosome 13 for WD, is only known in Iceland. In twenty healthy Icelandic heterozygotes for WD and their age- and gender-matched controls, copper concentration in plasma, ceruloplasmin (CP) concentration, CP oxidative activity and CP-specific oxidative activity in serum and superoxide dismutase (SOD1) activity in erythrocytes were determined. The same determinations were done on the five WD patients. There was no significant difference in these parameters between the heterozygotes and the controls, although an inclination toward lower CP determinations and higher SOD1 activity in the heterozygotes was noted. As expected the WD patients were low on the copper and CP parameters, but their SOD1 activity was within the upper normal range. In conclusion, the CP parameters and SOD1 activity are within the normal range in Icelandic heterozygotes for WD, although with a trend toward mild dyshomeostasis. This may indicate subclinical copper retention in the heterozygotes, but a bigger study group is needed to confirm this.

Glutathione peroxidase (GPX) activity in blood of ewes on farms in different scrapie categories in Iceland.

BACKGROUND: Preliminary studies indicated decreased glutathione peroxidase (GPX) activity in blood of ewes on scrapie-afflicted farms. Other studies have shown decreased GPX activity in brain of prion-infected mice and in prion-infected cells in vitro. The aim of this study was to examine the GPX activity in blood as well as the distribution of GPX-activity levels from ewes on farms in scrapie-afflicted areas in Iceland. METHODS: Blood samples were collected from 635 ewes (non-pregnant [n = 297] and pregnant [n = 338]) on 40 farms in scrapie-afflicted areas during the years 2001-2005, for analysis of GPX activity. The farms were divided into three categories: 1. Scrapie-free farms (n = 14); 2. Scrapie-prone farms (earlier scrapie-afflicted, restocked farms) (n = 12); 3. Scrapie-afflicted farms (n = 14). For comparison, 121 blood samples were also collected from non-pregnant ewes on one farm (farm A) in a scrapie-free area (scrapie never registered). Chi-square test was used to test for normal distribution of GPX-results, and Kruskal-Wallis test to compare GPX-results between categories. RESULTS: The GPX-results appeared to be biphasically distributed in ewes in all three scrapie categories and on farm A. The presumptive breaking point was about 300 units g Hb-1. About 30-50% of the GPX-results from ewes in all three scrapie categories were below 300 units g Hb-1 but only about 13% of the GPX-results from ewes on farm A. The mean GPX activity was highest on farm A, and was significantly lower on scrapie-prone farms than on scrapie-free or scrapie-afflicted farms (non-pregnant and pregnant ewes: P < 0.005, respectively; non-pregnant and pregnant ewes combined: P < 0.0005). CONCLUSIONS: 1) the distribution of GPX-results in blood of Icelandic ewes apparently has a biphasic character; 2) the GPX-results were higher in ewes on one farm in a scrapie-free area than in ewes on farms in the scrapie-afflicted areas; 3) GPX-activity levels were significantly lowest on earlier scrapie-afflicted, restocked farms, which might have a bearing on the recurrence of sporadic scrapie on these farms; 4) further study on the possible role of GPX activity in the occurrence of scrapie in Iceland is warranted.

Ceruloplasmin and superoxide dismutase (SOD1) in Parkinson's disease: a follow-up study.

In this follow-up study concentration, oxidative activity and specific oxidative activity of ceruloplasmin (CP) in serum and the activity of superoxide dismutase (SOD1) in erythrocytes were reexamined in 28 of originally 40 patients with Parkinson's disease (PD), and their age- and gender-matched controls. The mean CP and SOD1 parameters were significantly lower in the patients than in the controls. SOD1 activity and age of the patients were inversely correlated. The patients were divided into two subgroups based on their H&Y score i.e. groups II and III (12 patients) versus groups IV and V (16 patients). No significant difference was found in the CP or SOD1 parameters between the subgroups. Patients were also divided into two subgroups based on treatment with levodopa and decarboxylase blocker alone (12 patients) or given additionally a dopamine agonist (15 patients). No significant difference in the parameters was found between these subgroups in relation to intake of dopamine agonists. Results of this study are in agreement with results of the former study 5 years earlier. There is considerable overlap in individual values between patients and controls of the parameters studied. Thus CP and SOD1 have no obvious value for diagnosis or clinical evaluation of PD.

Temporal trends of organochlorine contamination in Black Guillemots in Iceland from 1976 to 1996.

The levels of several different persistent organochlorines (OCs) in Black Guillemots Cepphus grylle, collected during the summers of 1976-1996 at Breioafjörour in W-Iceland, were investigated. The levels of about 40 different organochlorines (PCBs, DDTs, chlordanes, toxaphenes, HCH, HCB) were compared with respect to age, sex, fat content, and year of collection. The levels of PCBs correlated very closely with those of DDE, indicating long-range transport as the major source of these contaminants in Iceland, with the ratio PCBs/DDE mostly in the range of 2-5. Unlike the Gyrfalcon Falco rusticolus, the organochlorine levels did not seem to accumulate substantially with age, neither in males nor females. The variation in the levels of OCs at the age of 2 years was even greater than the variation in OC levels over an age range of 12 years. In immature birds the levels of PCBs, DDE, HCB and beta-HCH declined very slowly (T(1/2) from 12 to 20 years) over the years 1976-1996, whereas the levels of alpha-HCH and p,p'-DDT declined much faster. The levels of trans-nonachlor, alpha-chlordane, gamma-chlordane, oxychlordane, and toxaphene did not correlate with the year of collection. As the Black Guillemot is mostly a resident seabird, feeding mainly on small fish and invertebrates, this investigation should give a good indication of the temporal trends of organochlorine pollution at Breioafjörour, Iceland, during this 20 year period and is likely to reflect baseline trends in the marine environment of the North-Atlantic Ocean.