was also correlated with CSF BACE1 activity (r⫽0.315, p⬍0.001) as well as CSF BACE1 protein level (r⫽0.149, p⬍0.05). Using CSF BACE1 level and activity, MCI patients can be distinguished from both AD and HC. Conclusion: Significant elevation of CSF BACE1 levels and activities in CSF of MCI patients is a predictor of early stage of AD. S4-01-04 ABETA-ANTIBODIES IN SERUM AND CSF AS POTENTIAL MARKER OF BIOLOGICAL ACTIVITY IN AD Yansheng Du 1 , Xing Wei 1 , Liming Zhao 1 , Richard Dodel 2 , Harald Hampel 3 , Martin Farlow 1 , 1 Indiana University, Indianapolis, IN, USA; 2 Friedrich-Wilhelms-University Bonn, Bonn,Germany; 3 Ludwig- Maximilians University, Munich, Germany. Contact e-mail: ydu@iupui.edu Background: Naturally occurring autoantibodies against amyloid ⫽ (A⫽ ) peptide have been identified in both CSF and serum from normals and patients with Alzheimer’s disease (AD). However, the role of these antibodies play in AD pathogenesis and whether they can used as biomarkers for AD remain unclear. Objective(s): Determining whether autoantibodies against A ⫽ can be used for diagnosis or treatment in AD. Methods: Autoantibodies against A ⫽ in human IVIG product were purified by affinity columns and injected into APP transgenic mice in different doses. The CSF and plasma levels of A ⫽ were analyzed using ELISA to determine the relationship of antibody levels and A ⫽ levels. Additionally, a study was performed to investigate the corre- lation between CSF and serum levels of autoantibodies and A ⫽ in humans. Result: Higherdoses ofautoantibodies against Ab were associated with increased plasma and decreased CSF levels of A ⫽ . However, lower doses of these antibodies had little effects on A ⫽ levels in either plasma or CSF. Moreover, human CSF and serum autoantibodies against A ⫽titers also did not correlate to the Ab levels. Conclusions: Human naturally occurring autoanti- bodies against A ⫽ can efficiently raise plasma A ⫽ levels from hypothesized brain sources. However, since low doses of these antibodies had little effect on A ⫽ levels, they may not be useful as an effective biomarker in early diagnosis and follow-up of AD. These antibodies appear to have potential as an immu- notherapeutic treatment for AD. S4-01-05 PEPTIDOMICS ANALYSIS OF CEREBROSPINAL FLUID FOR THE DETECTION OF POSSIBLE BIOMARKERS FOR ALZHEIMER’S DISEASE Hartmut Selle 1 , Harald Hampel 2 , Katharina Burger 2 , Klaus Hager 3 , Jens Lamerz 1 , Lars Lannfelt 4 , Matthias Riepe 5 , Michael Schrader 1 , Hayrettin Tumani 6 , Hans-Dieter Zucht 1 , 1 BioVisioN AG, Hannover, Germany; 2 Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany; 3 Department of Geriatrics, Henrietten Hospital, Hannover, Germany; 4 Uppsala University Hospital, Department of Public Health/Geriatrics, Uppsala, Sweden; 5 Clinic for Psychiatry and Psychotherapy, Charite´ Medicine Berlin, Berlin, Germany; 6 Department of Neurology, University of Ulm, Ulm,Germany. Contact e-mail: h.selle@biovision-discovery.de Background: The search for diagnostic markers for Alzheimer’s disease (AD) aims at a further improvement of the differential diagnosis of AD especially at the early presymptomatic state of the disease. Since peptides are degradation products and processed forms of larger proteins, they are possible products of neurodegenerative processes. The comparison of the comprehensive CSF peptidomes of AD patients and controls should iden- tify peptides correlated with AD pathogenesis. Objective: The compre- hensive analysis of the peptide profile of cerebrospinal fluid from Alzhei- merand control patientsallowsto compare the peptide patterns with respect to AD-specific processes. The main objective was the detection and identification of reliable and robust biomarkers specific for AD. Methods: Cerebrospinal fluid samples from patients with AD (n⫽140), with other forms of dementia (vascular, Lewy-body, frontotemporal dementia, Par- kinson’s disease, n⫽70) and from neurologic patients without cognitive impairment (n⫽102) were analysed using our differential peptide display® (DPD) approach. The diagnosis of AD was made in five hospital-based expertcentres in Germany and Sweden in accordance with ICD-10, DSM-IV or NINCDS-ADRDA criteria. The samples were analysed us chromatographic separation of peptides and small proteins combine mass-spectrometric analysis, allowing the simultaneous examination of several thousands of different compounds. The samples were analysed in four independent analytical sets and data were evaluated by a cross dation procedure. Non-parametric statistics and ROC curves (receiver operator characteristic) which represent sensitivity as well as speci a marker candidate were used to discriminate between the AD and control groups and to define possible marker candidates. Conclusio comprehensive peptide profiling of a large number of well-characte CSF samples for AD-specific biomarker candidates resulted in the d tion of 30 signals from the mass-spectrometric read out which discr between the AD and the control groups. Twelve candidates were ide as fragments of the possibly neuroprotective neuroendocrine protei and another one as the complement factor C3-derived C3f. The com tion of peptide profiling from CSF with a cross validation procedure yielded novel potential biomarkers with remarkable robustness and relation to AD pathophysiology. S4-01-06 STATE AND PERPECTIVES OF BIOMARKERS RESEARCH USING INNOVATIVE METHODS, NOVEL STUDY DESIGN, AND BIO-BANKING Kaj Blennow, Univ of Goteborg, Molndal, Sweden. Contact e-mail: kaj.blennow@neuro.gu.se The CSF is in direct contact with the extracellular space of the brain thus reflect biochemical changes in the brain. The CSF biomarkers total tau (T-tau), phospho-tau (P-tau) and ⫽ -amyloid 1-42 (A⫽ 42),have in numerous studies been found to have a high sensitivity as diagnostic markers Researchers have now set the focus on early diagnosis of AD, especially to evaluate if these CSF biomarkers may be of use to identify which pa mild cognitive impairment (MCI) will progress to AD, i.e. have incip and which will not progress, since they have a benign form of MCI. A new study will be presented in which 137 MCI cases were followed clinically for an extended time period (4-6 years). During follow-up, 57 casesprogressed to AD with dementia, while 56 MCIcasesdid not progress, and 21 developed other disorders. CSF samples were taken at baseline. The combination of CSF T-tau and A ⫽ 42/P-tau 181 ratio showed 95% sensitivity and 87% specificity to discriminate incipient AD from benign MCI cases and those progressing to other dementias. We suggest that CSF biomarkers will be of great use in clinical Phas on new therapeutic compounds in MCI cases, since it will allow iden of MCI cases with incipient AD. In contrast, inclusion of non-progres cases may reduce the possibility to identify a clinical effect of the dr CSF biomarkers may also be valuable tools to identify and monitor the biochemical effect of new candidate drugs in AD patients. CSF biom be regarded as “state markers”, reflecting the intensity of a specific process. One example of a state marker is CSF T-tau, which reflects the intensity of the neuronal degeneration. Additional information can b from “stage markers”, such as CT/MRT measurements of hippocamp phy, which reflect how far the neuronal degeneration has proceeded CSF biomarkers in treatment trials will also be presented. WEDNESDAY, JULY 19,2006 SYMPOSIA S4-02 MCI - FROM DIAGNOSIS TO THERAPEUTICS S4-02-01 OVERVIEW OF THE CONCEPT OF MCI Steven Trent DeKosky, University of Pittsburgh, Pittsburgh, PA, USA. Contact e-mail: dekoskyst@upmc.edu S69 Symposia S4-02: MCI - From Diagnosis to Therapeutics