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S Helisalmi

Publications and source records attributed to S Helisalmi.

46 records · Page 3Linked to original sources
PubMed1995

Apolipoprotein E polymorphism and Alzheimer's disease in eastern Finland.

Apolipoprotein E is a polymorphic protein defined by three alleles, epsilon 2, epsilon 3 and epsilon 4. An increased frequency of the epsilon 4 allele is associated with late-onset familial and sporadic Alzheimer's disease (AD). We studied 202 Finnish AD patients and 55 age- and sex-matched controls. AD patients were divided into four subgroups; sporadic early-onset, sporadic late-onset, familial early-onset and familial late-onset disease. We found no significant differences in the epsilon 4 allele frequency between the subgroups. However, all the subgroups differed in the frequency of epsilon 4 allele detection from the controls (P < 0.0001). In the late-onset patients, the age at onset decreased from 76 to 69 as the number of epsilon 4 alleles increased from 0 to 2.

Age of Onset↗
PubMed1995

Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes.

An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-beta-protein and tau protein in vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (-54% of control) and the right amygdala (-37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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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.

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PubMedDate not supplied

Selegiline treatment and the extent of degenerative changes in brain tissue of patients with Alzheimer's disease.

BACKGROUND: A beneficial effect of selegiline (L-deprenyl) in Alzheimer's disease (AD) has been reported in several clinical studies. METHODS: The brain tissue from 17 deceased patients, members of a double-blind clinical trial to assess the potential benefit of selegiline in AD, were analysed. FINDINGS: In our study, the decrease in the Mini-Mental State Examination (MMSE) scores during the progress of the disease had been significantly influenced by selegiline treatment. Prior to death, the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo. However, according to our results, none of the lesions critical for AD diagnosis, such as counts of senile/neuritic plaques, neurofibrillary tangles or beta-A4 load, were influenced by the selegiline treatment. INTERPRETATION: In conclusion, according to our study, mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment, leading to the functional benefit found in AD.

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PubMedDate not supplied

Alzheimer pathology of patients carrying apolipoprotein E epsilon 4 allele.

A recent report suggested that brains of Alzheimer patients homozygous for APOE epsilon 4 show increased amyloid pathology compared to APOE epsilon 3 homozygotes. We studied APOE allele frequencies in 73 AD patients and 38 controls. We also investigated relation of APOE genotypes to beta/A4 immunopositive plaques, cerebrovascular beta/A4 deposition, neurons expressing paired helical filaments (PHFs), and synaptophysin-like immunopositivity in 22 neuropathologically verified AD patients. We also correlated APOE genotypes of definite AD patients to beta/A4 immunoreactivity in dermal vessel walls detected in lifetime skin biopsy samples. APOE allele epsilon 4 frequency was increased in AD compared to nondemented controls (0.37 vs. 0.11; p = 0.006). The number of beta/A4 immunoreactive plaques, PHFs-containing neurons, the degree of cerebrovascular beta/A4 deposition or synaptophysin-like immunoreactivity did not differ significantly in AD patients with or without epsilon 4. beta/A4 deposition in dermal vessel walls was more frequent in definite AD patients with epsilon 4 (43%) than in patients without epsilon 4 (22%). However, the difference did not reach the statistical significance.

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PubMedDate not supplied

Spectral analysis of EEG in Alzheimer's disease: relation to apolipoprotein E polymorphism.

Apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for late-onset Alzheimer's disease (AD) and proposed to have a direct impact on cholinergic function in AD. Slowing of the EEG is characteristic in AD and the cholinergic system has an important role in modulating EEG. Fifty-eight AD patients at the early stage of the disease and 34 age- and sex-matched controls were studied using the quantitative EEG recorded from T6-O2 derivation. AD patients were divided into two subgroups: a) according to the ApoE allele (2 epsilon, 1 epsilon 4, and 0 epsilon 4) and b) according to familial aggregation. AD subgroups did not differ in clinical severity or duration of dementia. The AD patients with the epsilon 4 allele had higher relative theta amplitude and lower relative beta amplitude than controls and patients without the epsilon 4 allele. The peak frequencies were lower in all AD subgroups compared to controls. In conclusion, we found a tendency towards more pronounced EEG slowing in AD patients carrying the epsilon 4 allele. The minor differences in EEG may suggest differences in the degree of the cholinergic deficit in these subgroups.

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PubMedDate not supplied

M385T polymorphism in the factor V gene, but not Leiden mutation, is associated with placental abruption in Finnish women.

This study determines whether genetic variability in the gene encoding factor V contributes to differences in susceptibility to placental abruption. Allele and genotype frequencies of three single nucleotide polymorphisms (SNPs) in the factor V gene leading to nonsynonymous changes (M385T in exon 8, and R485K and R506Q [Leiden mutation] in exon 10) were studied in 116 Caucasian women with placental abruption and 112 healthy controls. Single-point analysis was expanded to haplotype analysis and haplotype frequencies were estimated using an expectation-maximisation (EM) algorithm. Comparison of single-point allele and genotype distributions of SNPs in exon 8 and exon 10 of the factor V gene revealed statistically significant differences in M385T allele (P = 0.021) and genotype ( P = 0.013) frequencies between the patients and the control subjects. The C allele of SNP M385T was significantly less frequent among the patients (7%) vs. the control subjects (13%), at an odds ratio of 0.48 (95% CI 0.25-0.91). Allele and genotype differences between the patients and control subjects as regards R485K and Leiden mutation were not significant. In haplotype estimation analysis, there was a significantly lower frequency of haplotype T-R-R encoding the T385-R485-R506 variant in the group with placental abruption vs. the control group (P = 0.038) at an odds ratio of 0.519 (95% CI 0.272-0.987). We conclude that T385 is less frequent among the patient group than in the control group. The M385T variant in the factor V gene other than the Leiden mutation may play a role in disease susceptibility.

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PubMedDate not supplied

Astrogliosis and the ApoE genotype. an immunohistochemical study of postmortem human brain tissue.

Significantly increased glial fibrillary acidic protein (GFAP) expression was seen in postmortem brain tissue from demented patients with Alzheimer's disease (AD) (73 cases, 61 females/12 males, mean age 84 +/- 9 years) compared to controls (22 cases, 10 females/12 males, mean age 78 +/- 9 years). In demented patients, the GFAP expression, counts of AD lesions, senile/neuritic plaques (SP/NP) and neurofibrillary tangles (NFT) were higher in patients carrying the apolipoprotein E (ApoE) epsilon4 allele compared to those without the ApoE epsilon4 allele. The astrogliosis correlated significantly with the counts of NFT in demented patients both with and without the ApoE epsilon4 allele. Furthermore, the astrogliosis correlated significantly with the counts of SP/NP, but this correlation, however, was influenced by the ApoE epsilon4 allele, being significant only in those cases without the ApoE epsilon4 allele. Our results demonstrate that not only the extent of AD lesions and GFAP expression, but also the relationship between AD lesions and the GFAP expression is influenced by the ApoE epsilon4 allele.

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PubMedDate not supplied

A longitudinal quantitative EEG study of Alzheimer's disease: relation to apolipoprotein E polymorphism.

Apolipoprotein E (apoE) sigma4 allele is a risk factor for late-onset Alzheimer's disease (AD) and is proposed to have an impact on cholinergic function in AD. Slowing of the EEG is characteristic in AD and the cholinergic system has an important role in modulating EEG. QEEG was recorded from 31 AD patients at the early stage of the disease and after a 3-year follow-up. AD patients were divided into subgroups according to the apoE sigma4 allele (2sigma4, 1sigma4 and 0sigma4). AD subgroups did not differ in clinical severity or duration of dementia. The AD patients carrying the sigma4 allele had more pronounced slow-wave activity than AD patients without the sigma4 allele, although the progression rate did not change. The differences in EEG may suggest differences in the degree of the cholinergic deficit in these subgroups.

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