elination to increase CSF levels of 24OHC. A dysfunction of BBB causes increased levels of 27OHC. Among patients with different CNS diseases, most had an increased level of at least one of the two oxysterols. Results: In CSF from 18 AD and 20 MCI patients the levels of 24- and 27OHC were significantly increased and 24OHC was significantly positively correlated with T-tau (r = 0.55, P 65 ng/L) and A42 ( 500 ng/L) were set according with literature. In case of AD, the percentage of patients with increased levels of 24OHC, T-tau, P-tau and decreased A42 were similar (ranging from 55 to 67%). In case of MCI, 50% of the patients had increased CSF levels of 24OHC, whereas only 18% and 24% of this population had increased levels of T-tau and P-tau. The high fraction of MCI patients with increased CSF 24OHC (50%), compared with the smaller number of the same patients with a significant alteration of the levels of the other markers, is consistent with the possibility that 24OHC is a new biomarker with a high negative predictive value in connection with evaluation of patients with cognitive impairment disease. P2-155 DEVELOPMENT OF SENSITIVE AND SPECIFIC ELISAS FOR THREE-REPEAT AND FOUR- REPEAT TAU ISOFORMS Connie Y. Luk 1,2 , Gavin Giovannoni 2 , Andrew J. Lees 1 , Rohan de Silva 1 , 1 Reta Lila Institute of Neurological Studies, London, United Kingdom; 2 UCL Institute of Neurology, London, United Kingdom. Contact e-mail: cluk@ion.ucl.ac.uk Background: Tau has been investigated in CSF as a potential diagnostic biomarker in neurodegenerative disorders associated with tau inclusions. Commercially available ELISA kits for quantification of total and phos- phorylated tau have shown increased CSF t-tau and p-tau levels in Alz- heimer’s disease. In other tauopathies such as FTDP-17, four-repeat (4R) isoforms are abnormally elevated in brain. In such cases, the quantity and ratio of three-repeat (3R) and four-repeat (4R) tau isoforms could be reflected in CSF and could potentially serve as an early diagnostic biomar- ker. Previously, we developed two monoclonal antibodies; RD3 and RD4, specific for 3R and 4R tau isoforms, and these were effectively validated in several neuropathological studies. Objective(s): To develop highly specific and sensitive ELISAs for three-repeat (3R) and four-repeat (4R) tau isoforms. Methods: The current study describes the development of both competitive and sandwich ELISAs for 3R and 4R tau isoforms using RD3 and RD4. Peptide-protein conjugates are used as plate coating anti- gens in competitive ELISAs. Recombinant 3R and 4R tau isoforms are used as standards to compete against the solid phase antigen for antibody binding. In the sandwich format, several polyclonal and monoclonal anti- bodies have been tested to capture the tau isoforms, while RD3 and RD4 are respectively used as detector antibodies. In both assay formats, HRP has been used as label for quantification of bound antibodies onto the solid phase. Results: The titres of RD3 and RD4 are found to be 1 in 150,000 and 1 in 6,000 respectively using peptide-protein conjugates as plate coating antigens. Both 3R and 4R tau isoforms are shown to effectively inhibit the binding of RD3 and RD4 towards the appropriate plate coating antigen in competitive ELISAs. We have achieved minimum detection limits for the tau isoforms in competitive ELISAs in the pg/mL range. Conclusions: Results of this study suggest that the current 3R tau and 4R tau ELISAs are feasible for rapid and sensitive detection of tau isoforms in CSF and corresponding biological matrices from patients with suspected tauopathies. These tests can potentially aid the diagnosis of tauopathies associated with differential expression of 3R and 4R tau isoforms. P2-156 BRAIN-DERIVED PROTEINS IN THE CEREBROSPINAL FLUID AND NEUROPATHOLOGICAL LESION PROFILES IN CJD Inga Zerr, Constanze Boesenberg-Grosse, Walter Schulz-Schaeffer, Georg-August University, Goettingen, Germany. Contact e-mail: IngaZerr@med.uni-goettingen.de Background: Neuronal and astrocytic proteins like 14-3-3, NSE, S-100, tau protein, phospho-tau protein and A1-42 were found to be altered in the cerebrospinal fluid (CSF) in patients with Creutzfeldt- Jakob disease (CJD). The pathogenetic mechanisms leading to these abnormalities are not known in detail, but a relation to rapid neuronal damage is assumed. However, no systematic analysis on brain derived proteins in the CSF and neuropathological lesion profiles has been performed to date. Objectives: To analyze brain derived proteins in the CSF and corresponding neuropathological lesion profiles using defined brain regions (five cortical, three subcortical and one cerebellar). Meth- ods: We used all case material available from 57 CJD patients identified between 1993 and 2003 in Germany to study this objective. CSF analysis was conducted between 3 and 4 weeks before death and subsequent autopsy. Levels of brain-derived proteins in the CSF were analyzed with respect to lesion severity as defined by a degree of spongiform changes, neuronal loss and gliosis. Results: We observed three different patterns of alteration of brain derived proteins in the CSF with respect to brain lesion profiles. NSE CSF levels were increased already with minor lesion severity and correlated with lesion severity of subcortical areas (thalamus, nucleus caudatus and putamen). Tau and 14-3-3 levels increased with minor pathological changes too, but a negative correlation could be observed with severity of cortical lesions. PrPc levels and A1-42 levels were normal at stages with minor lesions and correlated negatively with cortical pathology. The neuronal loss in temporal and occipital areas correlated best with declining A1-42 levels. Conclusions: Our results indicate that the alteration of levels of brain-derived proteins in the CSF does not simply reflect a neuronal damage but might also involve brain-area specific factors. In addition, the common assumption of a correlation between the degree of neuronal damage and CSF levels of brain-derived proteins has to be reconsid- ered, since this could not be observed for for some proteins such as NSE and tau. P2-157 EXPRESSION OF CSF AMYLOID BETA PEPTIDE PATTERNS ALZHEIMER’S DISEASE, DEMENTIA WITH LEWY BODIES AND PARKINSON’S DISEASE DEMENTIA Mirko Bibl 1 , Brit Mollenhauer 1 , Hermann Esselmann 1 , Piotr Lewczuk 2 , Hans-Wolfgang Klafki 2 , Katrin Sparbier 3 , Alexandr Smirnov 2 , Lukas Cepek 4 , Claudia Trenkwalder 5 , Eckart Ruther 1 , Johannes Kornhuber 2 , Markus Otto 4 , Jens Wiltfang 2 , 1 University of Goettingen, Goettingen, Germany; 2 University of Erlangen, Erlangen, Germany; 3 Bruker Daltronics, Leipzig, Germany; 4 University of Ulm, Ulm, Germany; 5 Paracelsus-Elena Klinik, Kassel, Kassel, Germany. Contact e-mail: mbibl@gwdg.de Background: Biomarkers are currently warranted to support the clinical differential diagnosis of dementias. The recently established A-SDS- PAGE/immunoblot enables a simultaneous quantification of amyloid-beta (A) peptides A1-37, 1-38, 1-39, 1-40 and 1-42 in cerebrospinal fluid (CSF). Objective(s): To investigate CSF of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) for disease-specific A peptide pattern. Methods: The A-SDS- PAGE/immunoblot was used to analyze the CSF of 23 patients with AD, 21 with DLB, 21 PDD and 23 non-demented disease controls (NDC). Results: A novel peptide with A-like immunoreactivity (A1-40*) aside the A peptide quintet was constantly observed in all 88 CSF samples investigated. We have characterized this peptide to represent an oxidized derivate of A1-40 using electrophoresis, immunodetection and MALDI- TOF analysis. Moreover, our data indicate an alpha-helical secondary structure of the peptide. AD and DLB shared a significant decrease of CSF A1-42 and a percentage elevation of A1-40*. The drop of CSF A1-42 was most pronounced for AD, whereas carboxterminally shorter A pep- tides (e.g. A1-37 and A1-38) tended to increase only in AD. The introduction of a ratio of A1-42 to A1-37 and A1-38, respectively, discriminated all diagnostic groups from each other, except DLB from S279 Poster P2: Monday Posters