Katalin Jakab

Apolipoprotein E polymorphism in Pick's disease and in Huntington's disease

The polymorphism of apolipoprotein E (apoE) has been recognized as a genetic risk factor in different neurodegenerative disorders, with or without tau protein- related neuropathology, but few published epidemiological data are available as concerns the association of different apoE alleles with two relatively rare forms of dementia, Picks disease (PiD) and Huntingtons disease (HD). In this study the frequency of the apoE4 allele was examined in 36 persons with histopathologically proven PiD and compared with that of the apoE genotype in 28 HD probands and 79 aged healthy controls. The E4 allele was overrepresented selectively in PiD (42%) as compared with the control population (7%). No such association was found for HD probands (9%). This finding lends further support to the hypothesis that the E4 genotype is not an Alzheimers disease specific susceptibility factor, and that it could be present in diverse dementing disorders with tau protein related neuropathology, such as PiD.

Somatosensory evoked potentials correlate with genetics in Huntington's disease

Abnormalities of somatosensory evoked potentials (SEPs) have been reported in Huntingtons disease, a neuropsychiatric disorder caused by the expansion of a CAG trinucleotide repeat. The aim of our study was to determine the relationship between these electrophysiological changes and the length of the nucleotide repeat. We found a striking correlation between the decrease in the early component amplitudes (N20 and N30) of the median nerve SEP and the repeat length, suggesting that these SEP alterations are indeed related to the genetically determined pathological process. The cortical components of the tibial nerve SEP exhibited a dram-atic alteration in the patient group and were the only SEP changes found in the group of asymptomatic carriers of the mutation, being more sensitive than the median nerve SEPs.

Analysis of CAG repeat expansion in Huntington's disease gene (it 15) in a Hungarian population

Huntington’s disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance. The genetic defect is a CAG trinucleotide repeat expansion at the 5′ end of the IT 15 gene on chromosome 4. This gene has not been analyzed in the Hungarian population yet. To obtain data DNA from 26 HD patients, 18 members of their families and 70 normal controls was amplified in the involved region by polymerase chain reaction. The CAG repeat numbers varied from 37 to 70 (median: 43) in HD patients and asymptomatic carriers, while individuals of the normal control group had 10–36 CAG repeat numbers (median: 18). The length of CAG repeat expansion in Hungarian HD patients was similar to that reported from other countries. The group of normal controls had the same CAG repeat expansion as populations reported from Western European countries. It is a useful piece of data for population genetics to prove that the population of Hungary is a mélange of different nations that influenced the history of the country in the last 11 centuries. As opposed to this, the only closely related nation, the Finnish, was genetically more isolated during this time, so the frequency of HD (and also the number of CAG repeats in normal individuals) proved to be exceptionally low.

Perceptual Categorization Is Impaired in Huntington’s Disease: An Electrophysiological Study

Recent evidence raised the possibility that the neostriatum and the corticostriatal circuits could play an important role in semantic categorization. In this study, we examined the electrophysiological correlates of natural scene categorization in Huntington’s disease (HD) patients and their asymptomatic relatives who were Huntington’s disease mutation carriers (HDC). Event-related potentials were recorded in HD patients, HDC subjects, and age-matched control subjects using a natural scene categorization task. The subjects had to decide whether a briefly presented image contained animals or no animals. Concerning the N1 component (150–250 ms), the mean amplitudes were more negative for nonanimal scenes as compared with stimuli containing animals at all electrode sites in the control group and at all but the lateral temporal electrode sites (T3, T4) in the HD group. Between-group comparison demonstrated that the N1 amplitudes were significantly smaller for both kinds of stimuli in the HD group in spite of a normal primary occipital component (P100). The HDC subjects were not significantly different from the controls concerning the N1 amplitudes. These results suggest that perceptual (N1) processes related to the categorization of natural scenes are specifically impaired in HD. The findings are in agreement with the hypothesis emphasizing the importance of neostriatal mechanisms in human categorization functions.

Alpha2-macroglobulin exon 24 (Val-1000-Ile) polymorphism is not associated with late-onset sporadic Alzheimer's dementia in the Hungarian population.

Several lines of biochemical evidence support a role of α 2-macroglobulin (A2M) in the pathogenesis of Alzheimers dementia (AD). A2M participates in the general defence mechanism against proteinases and it is supposed to be involved in the degradation of beta-amyloid peptide (β AP). Furthermore, A2M has been shown to reduce β AP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain. The exon 18 splice acceptor deletion polymorphism and the exon 24 (Val-1000-Ile) GG genotype were reported to be associated with AD, but the results are contradictory. Since the Hungarian population is genetically distinct from the other European ethnic groups, we examined whether the risk for developing AD is increased in the A2M GG carriers. The interaction of apolipoprotein E (apoE) and A2M polymorphisms was also examined. The distribution of A2M genotypes and alleles in the entire data set was consistent with the previous negative observations in which A and G allelic frequencies were comparable in both groups (72% and 28% in the AD population, and 72% and 28% in the control population, respectively). The GG genotype was over-represented (14%) only in the apoE ϵ 4 non-carrier subgroup of AD probands (7% in the control group), but the difference was not significant. Our data suggest that, although A2M has an important role in the AD-specific neurodegenerative process, its exon 24 Val-1000-Ile polymorphism is not likely to be associated with late-onset sporadic AD in the Hungarian population.

UVB irradiation-induced apoptosis increased in lymphocytes of Huntington's disease patients

Huntingtons disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the IT-15 gene coding for huntingtin. The mechanism of neuronal degeneration induced by the mutant huntingtin is not known. Apoptosis may play a role in it. Huntingtin is widely expressed in the cells, so abnormalities can be expected also in non-neural tissue. We examined the susceptibility of lymphocytes from HD patients, asymptomatic carriers and normal individuals to UVB irradiation-induced apoptosis. Lymphocytes from eight HD patients and two asymptomatic carriers showed increased apoptotic cell death compared to controls. Our results suggests that sensitivity of HD cells to induced apoptosis is not restricted to neurons.

Trunk alignment in different standing positions in healthy subjects and stroke patients -a comparative study with a simple method for the everyday practice.: Trunk alignment in healthy and stroke subjects

ABSTRACT Objectives: Weight-bearing (WB) on the lower extremities is an important outcome parameter in the rehabilitation of poststroke hemiparesis. However, the patients often regain this ability by compensatory movement patterns. Methods: Our goal was to characterize with a simple method the trunk alignment of healthy subjects and stroke patients (n = 17 for both groups) during standing and following lateral weight shift (WS). To describe trunk alignment, five markers were placed on the subjects’ back, and the angles of the trunk at both sides were defined by the lines drawn from the posterior angle of the acromion and the iliac crest on the same body side to the seventh thoracic spinal process. Weight distributions on the lower extremities during standing and lateral WS were determined with a force platform. Results: The patients had significantly limited WB capacity on their paretic limb, which was accompanied with significant asymmetry in the trunk alignment during standing and following WS to the paretic side. Discussion: Our results show that this patient population tends to use abnormal compensatory movement patterns to optimize weight shifting, and changes of trunk alignment play a key role in this. This should be taken into consideration during rehabilitation.

Determination of reference values of MDR-ABC transporter activities in CD3+ lymphocytes of healthy volunteers using a flow cytometry based method: MDR-ABC TRANSPORTER ACTIVITY VALUES IN CD3+ LYMPHOCYTES

MDR transporters are important biomarkers of drug resistance in cancer and in autoimmune conditions. We determined the MDR1, MRP1 and BCRP activity in CD3+ lymphocytes using a flow cytometry based method from 120 healthy volunteers in order to describe normal reference values of the activity of these transporters. The effects of gender and age were also determined.

Constraint-Induced Linguistic Therapy for Aphasic Patients in Hungary

Constraint-induced aphasia therapy is a widely used method in the treatment after stroke. Focusing on the theoretical basis of the original conception of the constraint-induced procedure we first made a special adaptation for Hungarian aphasic patients. We have been applying this method since 2012. So far, we have accomplished the treatment of 7 groups including 22 patients. It was supposed that the intensive language therapy based on the certain language features such as phonologic, semantic, syntactic and pragmatic parameters can facilitate the abstraction of general linguistic rules. The data were measured by standard and special tests significant improvement occurred in both the expressive and receptive language by the help of patients’ intact cognitive functions. Regarding our data we assumed that the new elaborated version for Hungarian language of the constraint-induced aphasia therapy can facilitate the abstraction and generalization of linguistic rules and could improve the patients’ linguistic skills according to the original method.

The role of cognitive training in the neurorehabilitation of a patient who survived a lightning strike. A case study

BACKGROUND Lightning-related injuries most often involve impairment of the functions of the central and peripheral nervous systems, usually including cognitive dysfunctions. We evaluated the cognitive deficit of a patient who had survived a lightning strike and measured the improvement after her cognitive training. This therapeutic method appears to be a powerful tool in the neurorehabilitation treatment. OBJECTIVE The aim of this case study was to prove the beneficial effects of cognitive training as part of the neurorehabilitation after a lightning strike. METHODS Six neuropsychological functions were examined in order to test the cognitive status of the patient before and after the 2-month cognitive training: phonological short-term memory (digit span test and word repetitions test), visuo-spatial short-term memory (Corsi Block Tapping Test), working memory (backward digit span test and listening span test), executive functions (letter and semantic fluencies), language functions (non-word repetition test, Pléh-Palotás-Lörik (PPL) test and sentence repetition test) and episodic memory (Rivermead Behavioral Memory Test and Mini Mental State Examination). We also utilized these tests in aged-matched healthy individuals so as to be able to characterize the domains of the observed improvements more precisely. RESULTS The patient exhibited a considerable improvement in the backward digit span, semantic fluency, non-word repetition, PPL, sentence repetition and Rivermead Behavioral Memory tests. CONCLUSIONS The cognitive training played an important role in the neurorehabilitation treatment of this lightning injury patient. It considerably improved her quality of life through the functional recovery.