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Biomedical subjects

O Heinonen

Publications and source records attributed to O Heinonen.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cerebrospinal fluid concentrations of soluble amyloid beta-protein and apolipoprotein E in patients with Alzheimer's disease: correlations with amyloid load in the brain.

OBJECTIVE: To compare soluble amyloid beta-protein and apolipoprotein E levels in cerebrospinal fluid (CSF) and brain extracts from patients with definite Alzheimer's disease. SETTING: University medical center. PATIENTS: Nineteen patients with definite Alzheimer's disease. MAIN OUTCOME MEASURES: Soluble amyloid beta-protein and apolipoprotein E levels in CSF, in neutral and low-pH brain extracts, and in formic acid-treated sections of the frontal, temporal, and cerebellar cortices, measured using enzyme-linked immunosorbent assay. RESULTS: Soluble amyloid beta-protein and apolipoprotein E levels in CSF were significantly lower in patients with congophilic angiopathy than in those without angiopathy. The levels did not correlate with the number of amyloid plaques in the neocortex. There was, however, a tendency toward an inverse correlation between the amount of amyloid beta-protein in the frontal cortex extracts and the soluble amyloid beta-protein level in CSF. CONCLUSION: Soluble amyloid beta-protein levels in CSF may reflect amyloid accumulation in brain blood vessels.

Aged↗
PubMed1996

Diagnostic accuracy of Alzheimer's disease: a neuropathological study.

This prospective study focused on the accuracy of diagnosis of Alzheimer's disease (AD). We recruited 100 dementia patients and 20 controls who underwent a systematic evaluation. The clinical diagnosis of probable AD or possible AD according to the NINCDS-ADRDA criteria was assigned in 69% of the patients, 21% had vascular dementia (VaD) (DSM-III-R) and 8% had mixed AD-VaD; only 2 patients (2%) had the Lewy body variant of AD (AD-LB). During a 3-year period 57 patients died, 53 of them (93%) being autopsied. Neuropathological examination according to the CERAD criteria showed definite AD in 27 out of 28 (96%) patients diagnosed as probable AD. In the possible AD group, the diagnostic accuracy was also high, 86% showed at least some degree of AD pathological alterations. The neocortical senile plaque scores correlated significantly with tangle scores in patients with AD pathology, and there was a significant negative correlation between age of onset and neocortical tangle scores. The concordance between the clinical diagnosis and pathological findings was clearly lower in VaD than in AD. In the clinical VaD group, 8 of 10 patients had at least some degree of AD changes together with vascular changes and only 2 of 10 patients had pure VaD. This study confirms the high accuracy of the NINCDS-ADRDA criteria for diagnosing AD. In contrast, uncertainty in the clinical diagnosis of VaD should be taken into account, for example, in drug trials with VaD patients.

Age of Onset↗
PubMed1995

Increased acetylcholinesterase activity in the CSF of Alzheimer patients carrying apolipoprotein epsilon4 allele.

We measured CSF acetylcholinesterase (AChE) activity in 57 Alzheimer's disease (AD) patients with different apolipoprotein E (apoE) genotypes at the early stage of the disease, and in 11 non-demented controls. The AChE activities of the whole AD group did not differ from those of controls. However, analysis of variance over the AD subgroups with two, one or no epsilon4 alleles and controls showed significant differences (p < 0.0001); the AD patients with two epsilon4 alleles had higher AChE activities than controls and AD patients with one or no epsilon4 and also the AD patients carrying one epsilon4 allele had higher AChE activities than the AD patients without the epsilon4 allele. The study suggests that cholinergic metabolism is altered in proportion to the number of apoE epsilon4 alleles. The different degree of AChE activity in relation to the number of epsilon4 alleles might have an impact on AD patients' responses to cholinesterase inhibitors.

Acetylcholinesterase↗
PubMed1995

Measurement of serum lipid peroxidation during exercise using three different methods: diene conjugation, thiobarbituric acid reactive material and fluorescent chromolipids.

Serum lipid peroxidation was measured by three different methods (diene conjugation, DC; thiobarbituric acid reactive material, TBARM; and fluorescent chromolipids, FC) during physical exercise of different duration. The aim of the study was to investigate which of the three methods is the most representative in measuring oxidative stress after physiological stimulus (physical exercise) in man. In general, diene conjugation is a measure of early events of lipid peroxidation reactions, TBARM measures end products of lipid peroxidation and FC are products formed by reaction of end products of lipid peroxidation with the amino groups. In trial I, 8 subjects ran 1 km with maximal speed; in trial II, 7 subjects ran 10 km with maximal speed; in trial III, 9 subjects ran 27 km with maximal speed, and in trial IV, 5 subjects cycled 8 days in competition, altogether 1061 km biking. In each trial venous blood samples were taken before and immediately after the exercise. In trials II, III, and IV serum DC concentration increased by 14% (P < 0.05), 11% (P < 0.01), and 25% (P < 0.05), respectively, during the exercise. FC or TBARM did not change in the trials. We conclude that DC as a measure of the early phase of lipid peroxidation may be less affected by protective antioxidant functions than FC and TBARM methods, which both measure end products of lipid peroxidation. Therefore, DC may be the most sensitive of the three methods to estimate serum lipid peroxidation induced by exercise in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer's disease.

We studied a synatophysin-like immunoreactivity in the hippocampal formation of patients with definite Alzheimer's disease, multi-infarct dementia, patients with no evidence of clinical dementia with neuropathological findings fulfilling the criteria of possible Alzheimer's disease, and age-matched nondemented controls. Possible Alzheimer's disease cases were of special interest because they were considered to represent early Alzheimer's disease. We also studied the spatial relationship of synaptophysin-like immunopositivity with amyloid-beta-protein immunopositive senile plaques and anti-paired helical filament immunopositive degenerating neurons locally as well as considering the intrinsic circuits in the hippocampal formation. The synaptophysin-like immunoreactivity was decreased in the hippocampus and the entorhinal cortex in patients with definite and possible Alzheimer's disease but not in multi-infarct dementia patients compared to controls. Equal loss of synapses in possible and definite Alzheimer's disease patients supports the hypothesis that synaptic loss is an early phenomenon in Alzheimer's disease. Unchanged synaptophysin-like immunopositivity in patients with multi-infarct dementia suggests that the loss of synapses is centrally involved in the pathogenesis of Alzheimer's disease and not dementia per se. There was no spatial correlation between loss of synapses and amyloid-beta-protein positive senile plaques. Moreover, we could not find a strict spatial relationship between senile plaques and degenerating neurons. Our results do not support the amyloid cascade hypothesis of Alzheimer's disease that local accumulation of amyloid-beta-protein leads to the loss of synapses.

Aged↗
PubMed1995

Serum selenium, zinc and copper in Swedish and Finnish orienteers. A comparative study.

Serum selenium, zinc and copper concentrations of 127 highly-trained Swedish orienteers have been analysed and compared with the corresponding values of 30 elite Finnish orienteers, and those of 111 healthy Finnish medical students. The mean serum selenium levels of Finnish orienteers, 1.35 mumol l-1, and students, 1.38 mumol l-1, were statistically significantly higher than those of Swedish orienteers, 1.09 mumol l-1. The serum levels of selenium were lower than 1.0 mumol l-1 in 27% of Swedish orienteers. This is obviously due to the lower selenium intake of the population in Sweden, where the soil selenium content is known to be low. Serum levels of zinc were within the reference interval in both Swedish and Finnish orienteers (mean values 14.8 and 14.1 mumol l-1, respectively). However, Finnish students had significantly lower serum levels of zinc, 12.5 mumol l-1. The mean serum concentration of copper was statistically significantly higher in females than in males.

Adolescent↗
PubMed1995

Relation of coronary atherosclerosis and apolipoprotein E genotypes in Alzheimer patients.

BACKGROUND AND PURPOSE: Apolipoprotein E (apoE) epsilon 4 allele has been associated with a high risk for coronary heart disease. Increased frequency of the epsilon 4 allele has also been reported in patients with late-onset familial and sporadic Alzheimer's disease (AD). The aim of this study was to investigate the degree of coronary and cerebral atherosclerosis in a neuropathologically verified series of AD patients with different apoE genotypes. In addition, we studied the relationship between the degree of coronary and cerebral atherosclerosis and the extent of beta-amyloid (A beta) accumulation. METHODS: We studied 38 subjects (32 patients with definite AD and 6 age-matched control subjects) for whom postmortem autopsy delay was less than 8 hours. ApoE genotypes were identified through Hha I digestion of the polymerase chain reaction-amplified samples. We used A beta immunohistochemistry to detect diffuse and neuritic plaques as well as cerebrovascular amyloid. The degree of coronary and cerebral atherosclerosis was rated as none, mild, moderate, or severe. RESULTS: The apoE genotypes of the AD patients were epsilon 4/4 2, epsilon 3/4 19, epsilon 3/3 9, and epsilon 3/2 2. We found more severe atherosclerosis of the coronary vessels among AD patients with the apoE epsilon 4 allele compared with those AD patients without the epsilon 4 allele (chi 2 = 4.1, df = 1, P < .05). The extent of cerebral atherosclerosis did not differ among AD subgroups with and without the epsilon 4 allele. The degree of coronary or cerebral atherosclerosis was not related to the amount of amyloid accumulation in the frontal and temporal cortices or in the hippocampal structures. CONCLUSIONS: This study confirms the association of apoE epsilon 4 allele with coronary atherosclerosis in AD patients.

Aged↗
PubMed1994

beta-Amyloid protein immunoreactivity in skin is not a reliable marker of Alzheimer's disease. An autopsy-controlled study.

OBJECTIVES: As a possible diagnostic marker for Alzheimer's disease (AD), we investigated beta-amyloid protein (beta/A4) immunoreactivity in skin. Furthermore, we studied the presence of beta-amyloid precursor protein 695 immunoreactivity in skin. DESIGN: Lifetime skin biopsy specimens were stained for beta/A4 and beta-amyloid precursor protein 695. The follow-up period was 12 months. We determined the correlation between beta/A4 immunoreactivity in skin and brain in patients with a neuropathologic diagnosis. SETTING: All patients with dementia were hospitalized; most of them had moderate to severe dementia. Aged nondemented controls were residents of a nursing home. The Down's syndrome (DS) group included both hospitalized and ambulatory patients. Young nondemented controls were medical students or staff members who volunteered for the study. PATIENTS AND OTHER PARTICIPANTS: The study included a total of 111 subjects. Thirty-five patients had probable AD, nine had possible AD, 15 had multi-infarct dementia, one had idiopathic Parkinson's disease, and one had Parkinson's disease and possible AD. There were also 19 elderly nondemented controls, 23 patients with DS, and eight young nondemented controls. MAIN OUTCOME MEASURES: Immunohistochemical detection of beta/A4 in skin and correlation to the diagnosis of AD. RESULTS: Immunopositivity for beta/A4 antibody was present in and around the endothelium of dermal blood vessels in a proportion of patients with AD and multi-infarct dementia as well as elderly controls. The patients with sporadic AD displayed beta/A4 immunoreactivity significantly more frequently than did patients with familial AD, patients with multi-infarct dementia, and controls. The beta/A4 immunopositivity in skin was rare in the patients with DS and not present in young controls. Instead, 48% of patients with DS but none of other groups had beta-amyloid precursor protein 695 immunoreactivity in skin. Only four (31%) of 13 patients with neuropathologically confirmed AD had shown endothelial beta/A4 immunopositivity in skin biopsy specimens while alive. CONCLUSION: Our results do not support beta/A4 as a diagnostic marker for AD.

Aged↗
PubMed1994

Testing for mutations in exon 17 of the beta-amyloid precursor protein gene in Finnish Alzheimer patients and normal subjects.

Mutations in the beta-amyloid precursor protein gene on chromosome 21 were shown to cause a small proportion of Alzheimer's disease. We studied the occurrence of the point mutations in exon 17 of the beta-amyloid precursor protein gene in a sample of Finnish familial Alzheimer patients and nondemented controls using polymerase chain reaction and a single strand conformation polymorphism technique. In addition, mutations in familial Alzheimer's disease patients were studied by sequencing the amplified products. Interestingly, two probable polymerase chain reaction errors were detected in codons 717 and 693 of the exon 17. However, no mutations in the exon 17 were confirmed adding the study to the body of literature that mutations in the exon 17 are a rare cause of familial Alzheimer's disease.

Age of Onset↗
PubMed1993

Circulating immune complexes in sera from patients with Alzheimer's disease, multi-infarct dementia and Down's syndrome.

Recent data suggest that immunological mechanisms may be implicated in the pathogenesis of Alzheimer's disease (AD). We tested the presence of circulating immune complexes (CIC) in the sera from dementia and Down's syndrome (DS) patients and age-matched controls using two methods: Clq-binding Elisa (ClqB-Elisa) and conglutinin-binding Elisa (KgB-Elisa). The probable AD and multi-infarct dementia (MID) patients had more frequently CIC in their sera as compared to elderly non-demented subjects (Chi-square; P < 0.05). The highest frequency of positive findings was detected for 10 DS patients (8 KgB-Elisa and 7 ClqB-Elisa positive) whereas only 1 of 10 young controls showed ClqB-positivity. In the AD patients the cognitive decline as assessed by the Mini-Mental Status test correlated significantly with CIC values. The study supports the view that systemic autoimmune mechanisms may be involved, at least partly, in dementing processes.

Adult↗