ical analysis. Results: In this study we showed the increased expressionlevels of GDNF in the brains of scrapie-infected mice on the days ofpost-inoculation (dpi) of 100 and 160. In addition, we found that moreintensive immunoreactivities of GDNF in the brains of scrapie-infectedmice, specifically in the hippocampal astrocytes, than in those of controlmice. Conclusions: This study suggest that up regulation of GDNF ex-pression in scrapie-infected brain may play a function to protect theneuronal cell loss and astrophy in neurodegenerative disorders, which isone of the important role in the pathogenic mechanisms of prion diseases.Acknowledgment: This study was supported by a grant of the KoreaHealth 21 R&D Project, Ministry of Health & Welfare, Republic of Korea.

P4-127 CSF NEUROFILAMENT LIGHT AS ADIAGNOSTIC AND PROGNOSTIC BIOMARKERFOR AMYOTROPHIC LATERAL SCLEROSIS

Henrik Zetterberg1, Johan Jacobsson2, Lars Rosengren3, Kaj Blennow1,Peter M. Andersen4, 1Neuroscience, Molndal, Sweden; 2ClinicalNeuroscience, Umeå University, Sweden; 3Neuroscience, Goteborg,Sweden; 4Clinical Neuroscience, Umeå University, Sweden. Contacte-mail: henrik.zetterberg@clinchem.gu.se

Background: Amyotrophic lateral sclerosis (ALS) is the most commonadult-onset motor neuron disease. The diagnosis is difficult to make,especially early in the disease process. Objective(s): To elucidate if cere-brospinal fluid (CSF) concentrations of neurofilament light (NFL) canserve as a biomarker for ALS, if there are differences in the concentrationof NFL between familial and sporadic forms of the disease and if NFLconcentration is related to disease duration. Methods: Seventy-nine ALSpatients (55 sporadic and 24 familial) were included and compared with acontrol group consisting of 206 unrelated patients with other neurologicaldisorders. CSF was obtained at the first neurological examination, analysedfor NFL and Abeta42 by ELISA and the results were compared to diag-nosis, apolipoprotein E (APOE) genotype and disease duration. Results:Median NFL concentration (range) was strongly elevated in ALS patientscompared to controls (2210 [255-10800] ng/L and 277 [�125-15506]ng/L, respectively, p�0.001). NFL levels were slightly lower among fa-milial cases compared with sporadic cases (1630 [291-10800] ng/L and2490 [255-10600] ng/L, respectively p�0.004). NFL concentration corre-lated inversely to disease duration (r�-0.352, p�0.005). Hence, high NFLlevels may predict rapidly progressive disease. Abeta42 levels were notdifferent in ALS compared to controls. Surprisingly, carrier status for theAlzheimer disease-associated APOE epsilon4 allele was associated withsignificantly lower NFL levels and longer disease duration after diagnosiscompared with non-carrier status (p�0.046 and p�0.023, respectively).However, when examining total disease duration, i.e. from the first symp-tom to death, this tendency disappeared (p�0.40), which may indicate thatAPOE epsilon4 carriers came to a diagnosis earlier than epsilon4-negativeindividuals. Conclusions: NFL may serve both as a diagnostic and prog-nostic biomarker for ALS.

P4-128 PHYSICAL TRAINING A NONPHARMACOLOGICAL METHOD OFTREATMENT IN P.D. PATIENTS

Floarea Revnic1, Nicolae Teleki2, Cristian Romeo Revnic3,Simion Revnic4, 1NIGG Ana Aslan, Bucharest, Romania; 2NIPMR,Bucharest, Romania; 3UMF CAROL DAVILA, Bucharest, Romania;4Assistance Medico-Social Center Mogosesti, Giurgiu, Romania. Contacte-mail: f_revnic@yahoo.com

Background: Physical kinetotherapy is a useful tool in prevention and oramelioration of pathological states and movement disorders. Objective(s):Evaluation of Physio kinetotherapy (PKT) method associated with medicaltreatment for P.D. patients in different evolutionary stages. Methods: 42patients aged (40-79) with P.D. evaluated clinically and neurologicallyhave been taken in our study. A three weeks PKT program has beenperformed, including thermotherapy, sedative massage applied before and

after PKT, for P.D. patients in stage II and III and also for immobilizedpatients along with electrotherapy and continuous magnetodiaflux. Re-sults: Out of 14 patients in stage IV on Hoehn & Yahr scale 6 achieved anamelioration of walking and 5 out of 10 patients in stage III improvedposture during walking. For P.D. patients in stage III, after 3 weeks PKT,9 out of 10 patients have recovered only one needed assistance for dressingup. Conclusions: PKT program is a useful tool along with medication inimproving control over gross motor movements such as walking, improv-ing posture and greater confidence in performing daily living activities.

P4-129 ALZHEIMER’S DISEASE: MOLECULARMECHANISM OF ANESTHETICS INDUCEDABETA PEPTIDE OLIGOMERIZATION USINGSPECTROSCOPY

Pravat K. Mandal1, Jay W. Pettegrew2, K. Panchalingam2,Ratna Mandal2, 1University of Pittsburgh Medical Center, Pittsburgh,PA, USA; 2University of Pittsburgh Medical Center, Pittsburgh, PA,USA. Contact e-mail: mandalp@upmc.edu

Background: Alzheimer’s disease (AD) is a significant contributor tocognitive decline and is responsible for half of the cases of dementia inlater life. Elderly patients frequently experience deterioration in cognitivefunction with long exposure to anesthesia during surgery and this isconsidered as a risk factor in AD. Recent studies indicate that anestheticscould promote oligomeric A� peptide formation and oligomerization (selfassociation) of A� peptides play an important role in AD. However, themolecular mechanism of anesthetic induced oligomerization of A� peptideis not yet known. Method: The interactions of anesthetics with halothaneare identified using multidimensional nuclear magnetic resonance (NMR)spectroscopy in membrane mimic environment. We have performed thefollowing NMR experiments: heteronuclear single quantum coherence(HSQC), three-dimensional nuclear Overhauser experiment, and total cor-relation experiment. We have followed the concentration dependent halo-thane effect on A� peptide structure, by adding a different amount ofhalothane. This biophysical study will be extended with other inhaled(isoflurane) and intravenous (thiopental and propofol) anesthetics. Theeffect of these four anesthetics to transgenic mice expressing excess A�

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peptide will also be studied to investigate the plaque forming ability ofthese anesthetics. This proposal will be performed in collaboration withdifferent faculty member’s within our Medical School. Results: Halothanespecifically interacts with G29, A30 and I31 residues (close to the kinkregion of the peptide) of both A�40 and/or A�42 peptide and facilitates A�

peptide oligomerization. Our study shows that A�42 is more prone tooligomerization than A�40 in the presence of anesthetics (Fig. 1). Futurebiophysical as well as animal studies with anesthetics will help us todetermine the neuroprotective anesthetics. Conclusions: To the best of ourknowledge, this is the first report providing molecular pathway of anes-thetic induced A� peptide structure alteration which may pose a risk factorfor elderly people. This research will open new avenues for drug discoveryfor neuroprotective anesthetics. Correspondence to Dr. Pravat Mandal.

P4-130 INCREASED AUTOPHAGY IS OBSERVED INNIEMANN-PICK DISEASE TYPE C CELLS

Seiya Ishibashi, Tsuneo Yamazaki, Koichi Okamoto, GunmaUniversity, Graduate School of Medicine, Maebashi, Gunma, Japan.Contact e-mail: seiyai@showa.gunma-u.ac.jp

Background: Niemann-Pick disease type C (NPC) is caused by disruptionof intracellular cholesterol transports, resulting in neurodegeneration. In-terestingly, neurofibrillary tangles (NFT) just observed in Alzheimer dis-ease (AD) are formed in cortical neurons of NPC patients. Thus, examiningthis disease might give a clue to understand the mechanisms causing AD.Objective: It is suggested that disorder of autophagic mechanisms isrelated with the pathogenesis in some degenerative diseases. Especially,increased autophagy is determined in chloroquine myopathy that is adisease model of inclusion body myositis (IBM). In IBM, intracellularvesicular compartments, which are indicated to be authophagic vacuolescontain phosphorylated tau. Thus, in IBM increased autophagy might berelated to form NFT. The purpose of this study is to examine whether thesame mechanism is involved in NPC. Methods: Autophagy was examinedby western blotting using an antibody raised against autophagosome mem-brane and also by monodansylcadaverine (MDC) uptake in mutant NPCcells and class 2 amphiphile treated cells demonstrating the NPC pheno-type. Results: Increased autophagic levels were observed in NPC mutantand drug treated cells compared to controls both by western blotting andMDC uptake. Conclusions: Increased induction of autophagy might berelated to the disease mechanisms of NPC.

P4-131 RELATIONSHIP BETWEEN DEMENTIA ANDPLASMA LEVELS OF ABETA40 AND ABETA42 INPATIENTS WITH DOWN SYNDROME - APROSPECTIVE, LONGITUDINAL STUDY

Harry Frey1,2, S.K. Herukka3, L. Heikkila4, T. Kivimaki4,T. Lehtimaki5, T. Pirttila6, 1Tampere Brain Research Center, Tampere,Finland; 2University of Tampere, Tampere, Finland; 3Dept. ofNeuroscience and Neurology, Univ of Kuopio, Kuopio, Finland; 4YlinenCentral Institution, Tampere, Finland; 5Dept. Clinical Chemistry, Univ.Tampere, Tampere, Finland; 6Dept. Neurol. Kuopio Univ. Hosp.,Kuopio, Finland. Contact e-mail: harry.frey@uta.fi

Patients with Down syndrome (DS) develop neuropathological changesconsistent with Alzheimer’s disease (AD) by the age of 40. It is hypoth-esized that the increased amyloid precursor protein (APP) gene dosage dueto a trisomy of chromosome 21 results in the overproduction of beta-amyloid protein (Abeta) and thereby to AD neuropathology. Previousstudies suggest that increased plasma Abeta levels may antecede develop-ment of AD in general population. Our aim was to examine whether plasmaAbeta levels are related to dementia in patients with DS.

We prospectively selected 30 cytologically confirmed DS patients of whom9 were demented and 21 nondemented at baseline. Neuropsychologicalevaluation and blood tests were done yearly during a 5-year period. Abetalevels were measured by ELISA. The APOE4 genotype was determined.

Quantitative neuropathological analyses were done in 11 patients who diedduring the study.

Plasma Abeta42 levels were substantially higher in both groups thanpreviously reported Abeta42-levels in non-DS individuals but no signifi-cant difference between the groups was observed. The Abeta40 levels arelower than Abeta42 levels in both groups. There was no significant differ-ence in the Abeta42/Abeta42 ratio between the groups. 6 patients becamedemented during the follow-up but Abeta levels did not correlate withdevelopment of dementia. APOE4 genotype did not affect Abeta levels.Moreover, the plasma Abeta levels and amyloid pathology in the brainwere not correlated.

Our findings showed that the APP overexpression in DS patients is re-flected in blood. However, plasma Abeta does not contribute to the devel-opment of dementia and amyloid pathology in the brain in DS patients.

P4-132 COGNITIVE IMPAIRMENT IN NON-DEMENTEDPATIENTS WITH PARKINSON’S DISEASE

Jae Kim, Min Park, Dong-A University Medical Centre, Busan,Republic of Korea. Contact e-mail: jwkim@mail.donga.ac.kr

Background: Parkinson’s disease (PD) is a neurodegenerative disorderthat represents cognitive impairment as well as motor symptoms. Even inthe early stage of PD, cognitive alterations can be demonstrated by carefulneuropsychological test. Objective(s): The aims of this study are to inves-tigate the pattern of cognitive impairment and the population of subtypes ofmild cognitive impairment (MCI) in PD. Methods: One hundred andtwenty two patients with PD and 35 control subjects participated in thisstudy. Patients with PD who had dementia clinically or K-MMSE scorebelow 25 points were excluded. Parkinsonian patients with severe motordysfunction to interfere with the tests were also excluded. They were allmatched for age (61.1�10.3 vs 61.4�8.4), education periods (8.8�4.9 vs8.8�4.5), and K-MMSE score (27.6�1.6 vs 27.5�1.5). All subjects wereevaluated using the Seoul Neuropsychological Screening Battery (SNSB).Statistic analysis was performed with ANOVA and chi-square test. Re-sults: Patients with PD performed worse in digit span backward, ReyComplex Figure Test, visual memory, semantic fluency, stroop test, andalternating hand movement test (p�0.05) compared with control group. OnSNSB test, 100 patients (82.1%) showed some abnormalities. Eighty-sixpatients (70.5%) showed frontal dysfunction, 47 (38.6%) memory impair-ment, 33 (27.0%) language dysfunction, 25 (20.5%) attention deficit and 22(18.3%) visuospatial dysfunction in the order of frequency. Eight patientswith PD showed single memory domain MCI and 28 single non-memorydomain MCI (20 frontal dysfunction). Multiple domain MCI was found in64 patients with PD (amnestic in 38 and non-amnestic in 26). Conclusions:It is concluded that, if specifically looked for, abnormalities of cognitivefunction can be detected very commonly in patients with PD. MCI in PDpatients is most frequently involved in the domain of frontal lobe function.

P4-133 DEMENTIA IN HERPETIC ENCEPHALITIS:COGNITIVE, BEHAVIORAL ANDNEUROIMAGING CHARACTERIZATION INRELATION TO DEGENERATIVE DEMENTIAS

Leonardo Caixeta, Candida Soares, Aluska Cruvinel, FederalUniversity of Goias, Goiania-GO, Brazil. Contact e-mail:leonardofcaixeta@yahoo.com.br

Background: Herpetic encephalitis must be, besides neurosyphilis, themost informative infectious disease in terms of cognitive and behavioralmanifestations, inviting parallels with primary degenerative dementias.Objective(s): To evaluate cognitive and behavioral aspects related toherpetic encephalitis and correlate dementia with neuroimaging pattern inpatients with this disease. Methods: Ten patients diagnosed with herpeticencephalitis, HIV negative, attended and followed at Tropical DiseasesHospital in Goiania, an institution linked to the Federal University ofGoias. Patients were evaluated in the following domains: cognitive eval-

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