Clinical Neuroscience

[Apolipoprotein E4 as a genetic risk factor in Alzheimer's Disease]

KÁLMÁN János1, JANKA Zoltán1

SEPTEMBER 20, 1996

Clinical Neuroscience - 1996;49(09-10)

[Apolipoprotein E (apoE) is a glycoprotein participating in the lipid transport and metabolism and in the neuronal regeneration processes. The gene of apo (APOE) is localized on the long arm of chromosome 19. The genetic polymorphism of APOE is manifested in three common alleles. The frequencies of these alleles, APOE2, APOE3, APOE4 are different in various human populations depending on their geographical origin. The APOE alleles have been considered to be responsible for the inter-individual variations of the serum cholesterol level. Besides its function in lipid transport, there are other relatively unknown but proven functions of apoE in the development of the nervous system and in peripheral nerve regeneration after injury. ApoE is considered as an important etiophathogenetic factor of atherosclerosis, familial hypercholesterolaemia and hyperlipoproteinaemia type III. The results of biochemical, molecular biological, population genetic and neuropathological examinations of the last three years have provided evidence that APOE4 alleles could be important risk factors of Alzheimer's dementia (AD). Recent findings regarding the relationship of apoE and AD are reviewed by the authors in connection with other aetiopathogenetic factors such as development of senile plaques, mutations of amyloid precursor protein gene, familial and sporadic forms of AD. These factors are discussed in relation to the therapeutic implications and dilemmas of genetic testing of APOE in AD.]


  1. Szent-Györgyi Albert Orvostudományi Egyetem Ideg- és Elmegyógyászati Klinika, Szeged



Further articles in this publication

Clinical Neuroscience

[Hemodynamic adaptation of fetal brain]


[Doppler color ultrasonography of the middle cerebral and umbilical arteries was performed on 104 fetuses born at term. A total of 254 investigations were carried out. Of the 104 fetuses studied, 52 infants had birth weights appropriate for gestational age (mean 3409.2 g) and 52 infants were small for gestational age (mean 2272.1 g). Cerebral hemodynamic adaptation was observed in growth retarded fetuses due to placenta! insufficiency. ln these cases the elevated umbilical vascular resistance evidenced the placenta! insufficiency. At the same time the decrease of the cerebral vascular velocimetry indexes indicated the improving cerebral blood supply. Only the systolic/diastolic ratio was significantly reduced in growth retarded fetuses when compared with normal controls. ln the umbilical artery the pulsatility index and systolic/diastolic ratio were raised significantly in growth retarded fetuses. The ratio of the cerebral arterial to umbilical cord artery index values proved a better indicator of the difference between growth retarded and normal controls than the index of the cerebral or umbilical artery alone. The ratios of all three index values of the growth retarded fetuses were significantly smaller than those of the normal controls (pulsatility index 1.03 versus 1. 60, resistance index 0.84 versus 1.19 and systolic/diastolic ratio 1.01 versus 2.02). The ratios of the small for date fetuses due to other, nonplacental causes were simi­ lar to the normal controls. The blood circulation disorder evokes hemodynamic adaptation in the feta! brain. The intrauterine growth restriction is a consequence of this disturbed blood supply. The cerebral circulatory adaptation failed in the small for date fetuses non associated with decreased blood supply.]

Clinical Neuroscience

[Distal Ulnar Neuropathies]

KISS Gábor, KÓMÁR József

[Compression of the distal part of the ulnar nerve is an uncommon entrapment neuropathy. Depending on the site of compression it may result in pure motor symptoms. The atrophy of the small hand muscles without sensory deficit may mimic motor neuron disease. Correct clinical examination and electrophysiology including measurement of ulnar distal motor latency to the first dorsal interosseous muscle can reveal the correct diagnosis. 46 surgically treated cases of distal ulnar neuropathy are reported. 12 patients had only muscle weakness without sensory abnormalities. 6 of them showed motor deficit restricted to the first dorsal interosseous and adductor pollicis muscles. 34 patients were followed up 31 of them improved, 3 cases should be reoperated because of recidive lipoma.]

Clinical Neuroscience

[Importance of sociological and psychological factors in pathogenesis of ischaemic stroke]

MENDE Lilla, JÓRI Birkás Adrien, FAZEKAS Gábor, FAZEKAS András

[The authors investigate sociological and psychological factors in the pathogenesis of ischaemic stroke, as a follow up of their earlier study. In the first part of the recent study patients and control subjects are compared in terms of frequency, severity, type and the temporal distribution of life events within the 5 years preceding the stroke. In the second part the importance of coping-style and psychological characteristics are studied. It is shown that the likely factors leading to stroke are: lower life events score in the more distant period, but higher life events score preceding the stroke, poor coping, greater emotional instability, trait-anxiety, hostility, and decreased job involvement. The type of life events, global Type-A behaviour, "speed and impatience", "hard driving and competitiveness” seem indifferent. On the basis of these results a successful stroke-programme should consider the complexity of somatic, sociological and psychological factors.]

Clinical Neuroscience

[Transoesophageal echocardiography after stroke]

NAGY Lajos, SÁMOCYI Marianna, TARJÁN Jenő, GARZULY Ferenc

[40 stroke patients were studied by both transoesophageal and transthoracic echocardiography. The diagnosis of stroke was based on medical history, physical examination and computerized tomographic brain scan. 39 patients underwent carotid duplex scan as well. Transoesphageal echocardiography was used to examine 40 patients of whom 19 had cardiac source of embolism. Out of these, 7 patients had definitive, whereas 12 had possible cardiac source of embolism. Transthoracic echocardiography was diagnostic only in 8 cases. Using carotid duplex scan, carotid stenosis was detected in 8 patients and sclerosis without significant stenosis in 8 others. From each of these two groups 4 patients had coexistent cardiac source of embolism as well. In the 8 patients with atrial fibrillation the left atrial thrombus and spontaneous echo contrast were more frequent than in patients with sinus rhythm. The transoesophageal echocardiography altered the management of antico agulation in 3 patients. The authors concluded that transoesophageal echocardiography is necessary in stroke patients.]

Clinical Neuroscience

[Prognosis of neuroepithelial tumours by means of cell proliferation studies]


[Cell-kinetic analysis of tumours has recently been widely used in clinical oncology for prognosis of patients treated with malignant neoplasms and for controlling the efficiency of treatment protocols. Definition of biological nature of neuroepithelial tumours was based on grading depending on the severity of cellular anaplasia. Neuroepithelial tumours can be characterized not only by the histological features but also by the DNA content and abnormalities of the cell proliferation – though the relationship between histological malignancy, proliferative activity and cellular aneuploidity was found to be rather controversial according to the literature. In this review article the clinical value of cell cycle analysis such as distribution of DNA content, DNA index; S-phase fraction; proliferation-markers [MIB 1 antibody, bromdeoxy uridin labelling index, mitotic index, definition of nucleolar organization region) are discussed on the basis of personal experience and review of the appropriate literature. Flow cytometry and examination of proliferation markers have a significant role in the definition of prognosis of patients suffering from WHO grade II and III neuroepithelial tumours. Gliomas giving rise to recidivism have a rapid cell cycle already at their first occurrence, which is characterized by raised proliferation indices, and occurrence of aneuploid cell clones. An unfavourable outcome can be prognosed in patients suffering from a WHO grade II or III glioma if the DNA index is above or below 1+0.1 if the value of the S phase fraction is above 6%, if more than 1 mitosis is found in 10 large magnification field, and if the number of cells labelled with MIB 1 antibody exceeds 3 in 1 large magnification field. The literature confirms our notion that further studies of proliferation characteristics may help in the production of a malignity score of gliomas that could support the efficiency of traditional histological grading in prognosis and control of complex therapy of these tumours.]

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Lege Artis Medicinae

[Human genome project]


[The main goal of the Human Genom Project is to reveal the complete structure of the human DNA, involving the sequence determination of the three billion basepairs. The program was launched in 1990, executed in laboratories of the public sector in several countries. Results of this project are made public on the Internet. In 1998 a private sector company, Celera, was founded with the same goal. In 2001 both projects announced the accomplishment of the first draft of the Human Genome. A whole issue of Nature and Science magazine was devoted to present the first results of their findings. According to the results less than one percent of the genetic information is transcribed to proteins. The estimated number of genes was also lower than expected (30-40 thousand, which number recently increased to 40-60 thousand). Based on these findings, human complexity should be ascribed to the variability of the information units (domains) rather than to the number of genes. Once the complete sequence of the humane genome is accomplished, the ’pre-genomic era’ will be over and the ’post-genomic era’ will begin, dealing with understanding the genetic information, annotating the genes and mapping the genetic variability of people.]

Lege Artis Medicinae

[The relationship between genetic polymorphism of apolipoprotein E and atherosclerosis and its relevance with clinical practice]


[The lipoprotein metabolism, having crucial role in atherogenesis is regulated by apolipo proteins, lipoprotein receptors and lipidtrans ferase enzymes. The genetic polymorphism of these proteins has been reported to be associated with lipid disorders. Beneath the rare forms (familial hypercholesterolemia, familial defective apo B syndrome) the most important monogenetic dyslipoproteinemia seems to be related to the apolipoprotein E polymorphism. The mean serum cholesterol concentration is influenced by the different apo E phenoytpes (E4 with high, E2 with low cholesterol level). In Hungary, the allele-frequencies (22 0,06, 22 0,80, 34 0,12) and the effect of apo E alleles on cholesterol concentration are very similar to the results found in other populations. Apo E polymorphism shows association with 1. hyperlipoproteinemia type III (E 2/2); 2. dyslipoproteinemia in familial hypercholeste rolemia (E2); 3. premature coronary heart disease (E4); 4. hypercholesterolemia in some populaton (E4); 5. insulin dependent diabetes mellitus in the Hungarian population (E2); 6. the rate of intestinal cholesterol absorption in some population (E4 with higher capacity). In such conditions the determination of apo E phenotype or genotype is very important to reveal the risks of the atherosclerosis and to asses the optimal hypolipidemic therapy.]

Clinical Neuroscience

Evaluation of the effectiveness of transforaminal epidural steroid injection in far lateral lumbar disc herniations

EVRAN Sevket, KATAR Salim

Far lateral lumbar disc herniations (FLDH) consist approximately 0.7-12% of all lumbar disc herniations. Compared to the more common central and paramedian lumbar disc herniations, they cause more severe and persistent radicular pain due to direct compression of the nerve root and dorsal root ganglion. In patients who do not respond to conservative treatments such as medical treatment and physical therapy, and have not developed neurological deficits, it is difficult to decide on surgical treatment because of the nerve root damage and spinal instability risk due to disruption of facet joint integrity. In this study, we aimed to evaluate the effect of transforaminal epidural steroid injection (TFESI) on the improvement of both pain control and functional capacity in patients with FLDH. A total of 37 patients who had radicular pain caused by far lateral disc herniation which is visible in their lumbar magnetic resonance imaging (MRI) scan, had no neurological deficit and did not respond to conservative treatment, were included the study. TFESI was applied to patients by preganglionic approach. Pre-treatment Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores of the patients were compared with the 3rd week, 3rd month and 6th month scores after the procedure. The mean initial VAS score was 8.63 ± 0.55, while it was 3.84 ± 1.66, 5.09 ± 0.85, 4.56 ± 1.66 at the 3rd week, 3rd month and 6th month controls, respectively. This decrease in the VAS score was found statistically significant (p = 0.001). ODI score with baseline mean value of 52.38 ± 6.84 was found to be 18.56 ± 4.95 at the 3rd week, 37.41 ± 14.1 at the 3rd month and 34.88 ± 14.33 at the 6th month. This downtrend of pa­tient’s ODI scores was found statistically significant (p = 0.001). This study has demonstrated that TFESI is an effective method for gaining increased functional capacity and pain control in the treatment of patients who are not suitable for surgical treatment with radicular complaints due to far lateral lumbar disc hernia.