clinical benefit of NSAID treatment over 12 months. Although this result may the associated with dosage or disease stage, it is our hypothesis that a proinflammatory endophenotype (PIE) at baseline is might identify a sub- group of patients who benefited from NSAID treatment. Methods: Base- line plasma samples were provided by the ADCS biospecimen bank from 209 participants. A total of 156 participants had viable samples for assay as well as available relevant data for inclusion. Biobank analysis of CRP and TNFa were conducted via electrochemiluminescence (ECL) using the Meso Scale Discovery platform. Results: Plasma levels of CRP and TNFa were utilized to define the PIE based on a priori criteria. The break- down of the PIE by treatment arm was as follows: Placebo - low ¼ 9.5%, middle ¼ 81%, high ¼ 9.5%; Naproxen - low ¼ 10%, middle ¼ 74%, high ¼ 16%; Rofecoxib - low ¼ 9%, middle ¼ 78%, high ¼ 13%. In these an- alyses we compared outcomes in patients with different levels of PIE at baseline. In the high PIE group, those on naproxen had significantly less decline in MMSE scores over 12 months, compared to those on placebo (partial eta squared ¼ 0.58; F[1,6] ¼ 8.2, p¼0.03; observed power ¼0.7). Indeed, 63% of the high PIE patients on naproxen remained stable or improved over 12 months, compared to 25% on placebo. Patients with a low PIE on naproxen appeared to decline faster than those on placebo group. There was no apparent treatment effect for the rofecoxib group. Conclusions: Baseline levels of a PIE identify a subgroup of participants that benefited from this clinical trial. As 10% of patients having a baseline high PIE, this profile may identify a substantial number of patients suffering from AD that benefit from naproxen treatment. This same profile may identify a subset of patients more likely to become worse with such treatment. O4-11-04 ACTIVE Ab IMMUNOTHERAPY CAD106 PHASE II DOSE-ADJUVANT FINDING STUDY: SAFETYAND CNS BIOMARKERS Ana Graf 1 , Marie-Emmanuelle Riviere 2 , Angelika Caputo 1 , Martin Rhys Farlow 3 , Giovanni Marotta 4 , Raquel Sanchez-Valle 5 , Philip Scheltens 6 , J. Michael Ryan 7 , Rik R. Vandenberghe 8 , 1 Novartis Pharma AG, Basel, Switzerland; 2 Novartis, Basel, Switzerland; 3 Indiana Universitty School of Medicine, Indianapolis, Indiana, United States; 4 Gerontion Research Inc., Toronto, Ontario, Canada; 5 Hospital Clinic, Barcelona, Spain; 6 VU University Medical Center, Amsterdam, Netherlands; 7 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States; 8 University Hospitals Leuven and University of Leuven (KUL), Leuven, Belgium. Contact e-mail: ana.graf@novartis.com Background: CAD106 is an active Ab immunotherapy in development for the treatment of Alzheimer’s disease (AD). Previous studies showed that doses up to 150mg CAD106 induced consistent Ab-antibody response with no major safety concerns. However, CNS biomarkers were not comprehen- sively assessed so far. Methods: Safety, tolerability and biomarker effects of CAD106 were assessed at doses of 150mg or 450mg in a 90-weeks dose-adjuvant finding study. Mild AD patients (MMSE 20-26) received up to 7injections of CAD106 or placebo (7:1 ratio) over 60 weeks with a full evaluation at week 78. Safety and antibody response compared CAD106 overall vs placebo; while biomarker analyses compared CAD106 strong serological responders (SSRs) vs non-responders + placebo (controls). Re- sults: 121 patients were enrolled to receive CAD106 (n¼106) or placebo (n¼15) and 8.5% vs 6.7% discontinued the study for a safety related reason, respectively. Two-thirds of CAD106-treated patients (150mg: 54%, 450mg: 76%) met the criteria for SSRs. Three SAEs were assessed as related to study medication by the investigator: acute psychosis, allergic dermatitis and atrial fibrillation. A total of five patients, all SSRs, had amyloid-related imaging abnormalities (ARIA), 4 with ARIA-H and 1 with ARIA-E, and all remained asymptomatic. Brief and self-limited injection-related reactions were observed in the majority of patients on active treatment. Within CAD106 group, signal with 18 F-florbetapir amyloid PET (SUVR of the global cortical region) correlated strongly (r¼ -0.8) with the AUC of Ab-IgG titers over 78 weeks. Amyloid load decreased over time in SSRs (n¼11) but not in controls (n¼4) with a group difference of -3.46% (95%CI: -31.04%, 24.12%). P-tau levels decreased in SSRs (n¼20) vs controls (n¼8), with a group difference of -5.13pg/mL (95%CI: -12.25, 1.99). Reduction in brain volume was more pronounced in SSRs (n¼54) over controls (n¼22) with a group difference for whole brain of -0.58% change from baseline (95% CI: -1.72, 0.55). No treatment effect was detected on the clinical scales for SSRs (n¼51) vs controls (n¼14). Conclusions: There were no unexpected safety findings related to the long-term exposure to CAD106-induced anti- bodies over 90 weeks. The pattern of biomarker data is consistent with the CNS activity of CAD106-induced antibodies in humans. O4-11-05 A PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PLASMA REPLACEMENT WITH 5% ALBUMIN IN BETA-AMYLOID PEPTIDE CLEARANCE IN CEREBROSPINAL FLUID, AND ITS EFFECTS IN PATIENTS WITH MILD- MODERATE ALZHEIMER’S DISEASE Merc e Boada-Rovira 1 , Oscar Lopez 2 , Laura N u~ nez 3 , Pilar Ortiz 4 , Fernando Anaya 5 , Isabel Hernandez 6 , Javier Olazar an 5 , Lluis Tarraga 6 , Mar Buendia 6 , Ramon P. Pla 7 , Isidro Ferrer 8 , Thomas Olabode Obisesan 9 , Joshua R. Shua-Haim 10 , Antonio P aez 11 , 1 Fundaci o ACE, Institut Catal a de Neuroci encies Aplicades, Barcelona, Spain; 2 University of Pittsburgh, Pittsburgh, Pennsylvania, United States; 3 Instituto Grifols S.A., Parets del Vall es, Spain; 4 Banc de Sang i Teixits, Barcelona, Spain; 5 Hospital General Universitario Gregorio Mara~ n on, Madrid, Spain; 6 Fundaci o ACE, Institut Catal a de Neuroci encies Aplicades, Barcelona, Spain; 7 Blood and Tissue Bank, Barcelona, Spain; 8 Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain; 9 Howard University, Washington, District of Columbia, United States; 10 Mid-Atlantic Geriatric Association, Manchester, New Jersey, United States; 11 Instituto Grifols, Parets del Vall es, Spain. Contact e-mail: mboada@fundacioace.com Background: Abnormal Ab protein metabolism and neurofibrillary tangle formation are the central pathology of Alzheimer’s disease (AD). Because there is a dynamic equilibrium between brain and plasma Ab levels, plasma exchange (PE) could remove the toxic Ab proteins, and provide clinical ben- efits. This study was conducted to determine whether PE therapy can modify the concentration of Ab and total and pTau in CSF and Ab in plasma. Methods: The study enrolled 42 patients with mild-moderate AD who were assigned to PE (using central catheter) or placebo (sham catheter); 37 completed the study (18 treated and 19 on placebo). Patients received 2 PE per week during three weeks, followed by one PE every week during 6 weeks, and one PE every two weeks for 12 weeks. After the last PE, all patients were followed for 24 weeks. Plasma amyloid levels were deter- mined before and after each PE session, and CSF was obtained four times during the course of PE, and twice after the cessation of the treatment. Cognitive measures included the ADAS-Cog, the MMSE, and a battery of neuropsychological tests. Activities of daily living (ADLs) were examined with the ADCS-ADLs scale and psychiatric symptoms with the Neuropsy- chiatric inventory (NPI). Results: Ab-42 levels increased in CSF and decreased in plasma in the PE group compared to placebo. CSF tau levels were not altered by PE. The ADAS-Cog scores showed no statistical differ- ences between groups, and the MMSE scores tended to be higher in the PE than in the placebo group. However, PE treated patients performed better on language and memory function tests compared to placebo, and the effect persisted after the discontinuation of the treatment. The ADCS-ADLs and the NPI scores were worse in the treated group compared to pacebo, although the difference subsided when PE was discontinued. Conclusions: This Phase 2 study showed that PE can alter Ab-42 levels in CSF and plasma. Although patients treated with PE had a decline in ADLs during the treatment period, they exhibited a persistent improvement of language and memory function tests, which suggests that further investigation of PE as treatment for AD is warranted. Oral Sessions: O4-11: Clinical Trials II: Anti-Amyloid and Inflammation P274