PIN1 gene variants in Alzheimer's disease.

BACKGROUND: Peptidyl-prolyl isomerase, NIMA-interacting 1 (PIN1) plays a significant role in the brain and is implicated in numerous cellular processes related to Alzheimer's disease (AD) and other neurodegenerative conditions. There are confounding results concerning PIN1 activity in AD brains. Also PIN1 genetic variation was inconsistently associated with AD risk. METHODS: We performed analysis of coding and promoter regions of PIN1 in early- and late-onset AD and frontotemporal dementia (FTD) patients in comparison with healthy controls. RESULTS: Analysis of eighteen PIN1 common polymorphisms and their haplotypes in EOAD, LOAD and FTD individuals in comparison with the control group did not reveal their contribution to disease risk.In six unrelated familial AD patients four novel PIN1 sequence variants were detected. c.58+64C>T substitution that was identified in three patients, was located in an alternative exon. In silico analysis suggested that this variant highly increases a potential affinity for a splicing factor and introduces two intronic splicing enhancers. In the peripheral leukocytes of one living patient carrying the variant, a 2.82 fold decrease in PIN1 expression was observed. CONCLUSION: Our data does not support the role of PIN1 common polymorphisms as AD risk factor. However, we suggest that the identified rare sequence variants could be directly connected with AD pathology, influencing PIN1 splicing and/or expression.

Antigen-antibody dissociation in Alzheimer disease: a novel approach to diagnosis.

With the ever-increasing population of aged individuals at risk of developing Alzheimer's disease (AD), there is an urgent need for a sensitive, specific, non-invasive, and diagnostic standard. The majority of efforts have focused on auto-antibodies against amyloid-beta (Abeta) protein, both as a potential treatment, and a reliable biomarker of AD pathology. Naturally occurring antibodies against Abeta are found in the CSF and plasma of patients with AD as well as healthy control subjects. To date, differences between diseased and control subjects have been highly variable. However, some of the antibody will be in preformed antigen-antibody complexes and the extent and nature of such complexes may provide a potential explanation for the variable results reported in human studies. Thus, measuring total amounts of antigen or antibody following unmasking is critical. Here, using a technique for dissociating antibody-antigen complexes, we found significant differences in serum antibodies to Abeta between AD and aged-matched control subjects. While the current study demonstrates the relevance of measuring total antibody, bound and unbound, against Abeta in AD, this technique may be applicable to diseases such as acquired immune deficiency syndrome and hepatitis B where determination of antigen and antibody levels are important for disease diagnosis and assessing disease progression.

[Dementive patients' caregivers--psychological aspect of their needs]. / Reakcje emocjonalne opiekunów osób z demencja--potrzeba pomocy spolecznej.

Patients with dementia, especially with dementia in the course of Alzheimer's disease require long-time care. In Poland, 92% of patients with Alzheimer's disease stay at home--mostly because of lack of qualified, easy-available care centers. An informal care is usually provided by patients' close relatives. The aim of the research was to assess how caregivers deal with everyday care problems, especially the psychical and social ones. The study was conducted in 1999 by the method of anonymous inquiry in the group of 42 caregivers, mostly members of Lublin's Alzheimer Association. The caregivers are children (53.6%) or spouses of patients (39.8%). In 61% of cases patient lives with the carer's family. 72% of our respondents consider their work as very hard. The care takes them seven days a week, 77% of carers have no possibility of rest. Almost half of respondents (47%) constantly feel depressed and tired. 15% claim that they hardly cope with nursing. 39% of caregivers have the feeling of deep, internal exhaustion.

Intimate partner violence by men abusing and non-abusing alcohol in Poland.

Alcohol use is to one of the most of risk factors for intimate partner violence. The aim of this study was to check the difference of demographic characteristics and type of violence between of the perpetrators with a history of alcohol abuse (A) versus the perpetrators without a history of alcohol abuse (N). Data were obtained from the survey conducted in the office of the Association for Violence Prevention in the city of Lublin, Poland. 400 perpetrators and their victims (400 subjects) were examined. To collect information from victims a specially designed questionnaire was used (VQ). Besides, another questionnaire (PQ) and The Alcohol Use Disorders Identification Test (AUDIT) was used to measure alcohol use in the perpetrators. About 76% of the perpetrators scored 8 and above (AUDIT). 84.8% of the perpetrators with a history of alcohol abuse (A) versus 9.2% of the perpetrators without a history of alcohol abuse (N) committed acts of violence after alcohol consumption. The A-perpetrators were more likely to be younger, have lower education and break law, and less likely to have permanent jobs than the N- perpetrators. The significant difference in the type of violence was found: the A-perpetrators were more likely to commit physical violence (78.2%) than the Nperpetrators (33.2%) and the N-perpetrators were more likely to commit sexual violence (32.2%) than A-perpetrators (9.14%). We would like to conclude that despite similarities among perpetrators, they are not a homogenous group so different therapeutic approach should be considered.

Co-existance of toxoplasmosis and neuroborreliosis - a case report.

The 53-year-old woman was initially diagnosed with multiple sclerosis, despite the fact that she did not really meet the clinical criteria. Her only symptoms were clumsiness and weakness of the right extremities. Being a veterinary research worker she had been exposed to infectious material. In 1995, she was diagnosed with ELISA as having toxoplasmosis and treated as such. In 2002, after the infectious, flu-like disease, she revealed arthritis and drowsiness, also with memory and language impairment. The patient continued to have symptoms consistent with previously examined clumsiness. She was diagnosed with Lyme via ELISA and PCR, and treated. She made a full recovery from acute symptoms. After a few months, neurological and neuropsychological examinations were performed. On the background of mild cognitive decline apraxia and difficulties of attention were noted as the main problems. A apraxia of the right hand complicated the patient's life and depreciated her quality of life. The patient underwent MRI examination. FSE, FAST and FLAIR sequences were made. The MRI demonstrated the appearance of several small hyperintense lesions in the white matter of the left and right frontal and left parietal lobe. These lesions were typical of the post-inflammatory leucoencephalopathy. Additionally, a ring-shaped, low-intensity lesion in the posterior part of the left parietal lobe was noticed. The lesion was 8 mm in diameter and described to be an old toxoplasmosis lesion. The patient had been treated and the symptoms consistent with Lyme disease resolved. Patient continues to have symptoms consistent with focal destruction of the parietal lobe. Over the past six months, she has not progressed and relapsed in a manner that is consistent with MS.

Nociceptin, OP4 receptor ligand in different models of experimental epilepsy.

The anticonvulsive activity of nociceptin, endogenous OP4 receptors agonist was investigated in pentylenetetrazole (PTZ), N-methyl D-aspartic acid (NMDA), bicucculine (BCC) and electrically evoked seizure models of experimental epilepsy. Nociceptin, at the dose of 10 nmol, suppressed the clonic seizures induced by PTZ, NMDA and BCC. [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 which has been proposed to be selective antagonist OP4 receptors, did not prevent the action of nociceptin. The effect of [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 on seizures induced by PTZ, NMDA and BCC was very similar to that of nociceptin. These data support the hypothesis that it possesses agonistic properties. Naloxone did not reverse the anticonvulsive action of nociceptin as well as [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 which excludes the participation of opioid receptor in this action. On the other hand in the electroconvulsive model of generalized seizures, nociceptin as well as [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 influenced neither the electroconvulsive threshold nor the maximal electroshock test. The data suggest that nociceptin and [Phe1(psi)(CH2-NH)Gly2]nociceptin-(1-13)-NH2 can exert anticonvulsive action. These properties depend on OP4 but not opioid receptors activation.

[Chronic fatigue syndrome following tick-borne diseases]. / Zespól przewleklego zmeczenia u pacjentów po przebyciu chorób przenoszonych przez kleszcze.

The chronic fatigue syndrome (CFS) is characterized by a feeling of tiredness persisting for over 6 months, associated with a number of other symptoms including headaches, myalgia and arthralgia, memory and concentration impairment. Its cause is unknown, there are neither objective diagnostic methods, nor causal treatment of the condition. In view of hypotheses suggesting a relationship between CFS and infections, 86 patients with a history of borreliosis or tick-borne encephalitis were examined. In 50% of these cases CFS could be identified. This clinical pattern was found in as many as 71% of the borreliosis patients, while only 24% of those with history of tick-borne encephalitis were diagnosed with CFS. Moreover, in the patients with a history of borreliosis after symptomatic treatment recommended for CFS, an amelioration was noted in as many as 61% of the cases. The findings suggest that the chronic fatigue syndrome is frequent among patients with a history of borreliosis.

Application of Choynowski's Memory Scale in assessment of patients with dementia.

INTRODUCTION: Neuropsychological assessment of patients with dementia necessitates the use of varied memory tasks designed to measure different memory processes, including information memorization, retention and retrieval. A valid memory battery should be demonstrated to discriminate between demented and non-demented subjects and its scores should be related to the degree of intellectual impairment. The objective of this study was to evaluate the potential usefulness of Choynowski's Memory Scale in assessment of patients with dementia. MATERIAL AND METHODS: Thirty-two patients with dementia and 64 age- and gender- matched healthy controls took part in the study. All participants were examined by means of Choynowski's Memory Scale, and the patients were additionally assessed by the Mini Mental State Examination and Clock Drawing Test (CDT). RESULTS: All subtests of Choynowski's Memory Scale were found to highly significantly (p ≤ 0.001) discriminate between patients with dementia and healthy controls. Except for Digit Span, all other subtests of Choynowski's battery were highly correlated with the global mental status as assessed by MMSE with correlation coefficients ranging from 0.59 to 0.81. Most subtests of Choynowski's Memory Scale were also moderately or highly correlated with performance on the CDT, and the correlations coefficients between the total score on Memory Scale and the CDT were r = 0.66 and r = 0.61 (p ≤ 0.001) for the free recall drawing and copying, respectively. CONCLUSIONS: Choynowski's Memory Scale showed high discriminative properties and strong associations with the degree of intellectual impairment in dementia. The results encourage the use of this battery in clinical settings.

Mutation screening of the MAPT and STH genes in Polish patients with clinically diagnosed frontotemporal dementia.

Frontotemporal dementia (FTD) is a common neurodegenerative disorder and is connected with about 10% of all dementias. In approximately half of all FTD cases, a positive family history has been reported. To date, several mutations at the tau protein gene (MAPT) were identified causing familial and sporadic FTD. Extensive polymorphic variability at the MAPT gene has also been shown to be a risk factor in progressive supranuclear palsy (PSP). The recently described gene Saitohin (STH), located in the intron 9 of MAPT gene, was also reported to be polymorphic. In the present study 23 unrelated Polish patients with clinically defined sporadic and familial FTD were screened for mutations at the MAPT gene. No pathogenic mutations were found in the group. Several novel silent intronic and exonic mutations were identified, most of them associated with two common haplotypes. In the reported group no correlation between extended MAPT haplotype and APOE genotype was determined. There was also no observed relation between age of onset and APOE status. At the STH gene only a common polymorphic change was found. It is postulated that MAPT mutations are not connected with most of the FTD cases in the Polish population.

Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland.

Mutations in three causative genes have been identified in patients with an autosomal-dominant form of early-onset Alzheimer's disease (EOAD). To determine the spectrum of mutations in a group consisting of 40 Polish patients with clinically diagnosed familial EOAD and 1 patient with mild cognitive impairment (MCI) and family history of AD, we performed a screening for mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) genes. Four previously recognized pathogenic mutations in PSEN1 gene (H163R, M139V) and APP gene (T714A, V715A), and three novel putative mutations in PSEN1 gene (P117R and I213F) and PSEN2 gene (Q228L) were identified. The 34 patients with no mutations detected were older than the patients with mutations. A frequency of APOE4 allele was higher in this group. Frequency of mutations is relatively low (17%), possibly due to used operational definition of a patient with familial EOAD (a patient having at least one relative with early-onset dementia). It could be concluded that screening for mutations in the three genes could be included in a diagnostic program directed at patients with a positive family history or age of onset before 55 years.