Background: Though functional imaging shows decreases in cerebral metabolism in established Alzheimer’s Disease (AD), studies using acti- vation paradigms in persons at-risk by virtue of apolipoprotein E genotype, family history, or mildly impaired status suggest a compensatory increase in perfusion prior to the development of overt dementia. Persons at-risk for young-onset AD by virtue of fully-penetrant mutations causing familial Alzheimer’s disease (FAD) allow us to sensitively evaluate the presymp- tomatic stage of the disease. In the current study we studied early changes in brain physiology using blood oxygen level dependent (BOLD) fMRI in presymptomatic persons destined to develop FAD by virtue of PSEN1 and APP mutations. Methods: Twenty-three presymptomatic persons (88% female) at-risk for inheriting a PSEN1 (n = 17) or APP (n = 6) mutation and one unrelated control underwent BOLD fMRI imaging during a block design, unrelated word pair memory task. FMRI was performed on a 3T Siemens Allegra Scanner using an EPI sequence with TR of 2500 and TE of 35 ms. BOLD signal during combined encoding and recall blocks, encoding only, and recall only were compared to that during distraction blocks. Genetic testing was performed and activation patterns compared between all mutation carriers (MCs) and non-carriers (NCs) as well as between younger and older subgroups based on a median split of MCs. All fMRI analyses were performed using FSL version 3.2. Results: Fifteen MCs (mean age 29 years) were compared to 9 NCs (mean age 34). Overall, there were no differences between the groups with regard to BOLD activation during the memory task. When the older group of 7 MCs (mean age 34) was compared to the 7 oldest NCs (mean age 40), MCs demon- strated decreased activation in the left medial parietal lobe maximal in the precuneus (Talaraich -12, -56, 30) during encoding + recall blocks relative to the NCs. Conclusions: FAD MCs not yet demonstrating cognitive impairment have less perfusion of the left precuneus during memory encoding and recall relative to baseline compared to NCs. We did not find evidence supporting a compensatory increase in cerebral perfusion in this presymptomatic population using this protocol in this population. P1-283 DIRECT VISUALIZATION OF -AMYLOID PLAQUES IN HYPERCHOLESTEROLEMIC RABBITS USING CLINICAL FIELD-STRENGTH MAGNETIC RESONANCE IMAGING John Ronald 1 , Yuanxin Chen 1 , Lisa Bernas 1 , Robert Hegele 1 , Kem Rogers 2 , Brian Rutt 1 , 1 Robarts Research Institute, London, ON, Canada; 2 University of Western Ontario, London, ON, Canada. Contact e-mail: jronald@imaging.robarts.ca Background: Definitive diagnosis of Alzheimer’s disease (AD) requires postmortem pathologic demonstration of beta-amyloid (A) plaques. The ability to non-invasively image A plaque burden would markedly im- prove the diagnosis and treatment of AD patients. This has been accom- plished in several transgenic mouse models using animal-dedicated high- field (7 or 9.4 T) MRI scanners. However, to determine the translational potential of MR techniques, it is important to visualize plaques using clinical field-strength (3T) scanners in larger animal models. Rabbits fed high (2%) cholesterol (CH) diets form A plaques, but plaque progression is hard to track due to a high mortality rate (liver failure). Here we show that low-level CH-feeding in rabbits resulted in a low mortality rate whilst still promoting the formation of A plaques. In addition, we developed a state-of-the-art clinical field MR technique allowing direct visualization of these plaques. Methods: Rabbits were fed a low (0.25%) CH (n=5) or normal (n=4) diet for 27 months. Ex vivo MRI of brains was performed on a 3T MR scanner interfaced with customized gradient and RF coils. 66x66x100 m3 MR images were acquired in 96 minutes. A-42 immu- nostaining and Prussian blue iron staining were performed on matched brain sections. Results: MR images revealed distinct signal voids through- out the brains of the CH-fed animals, located primarily in the hippocampus and adjacent cortex, striatum and thalamus (Fig. 1A). Voids correlated directly to small clusters of A-42-positive plaques, which were also consistently identified as iron-loaded (the presumed source of MR contrast) (Fig. 2). Minimal voids and plaques were seen in control brains (Fig. 1B). Conclusions: Our findings combine for the first time a large animal model of AD with clinical field MRI, and demonstrate direct visualization of A plaques. The low CH diet used resulted in both significant A plaque burden and a survivable model, allowing treatment effects after disease establishment to be assessed in the future. Extension of these technologies to an in vivo setting is practical, and should allow the study of AD pathogenesis in animals over time. These exciting results also hint at the promise of clinical MRI-based detection of A plaques in humans. P1-284 IN VIVO IMAGING OF AMYLOID DEPOSITION IN ALZHEIMER’S DISEASE USING THE NOVEL RADIOLIGAND [ 18 F] AV-45 Paul B. Rosenberg 1 , Y. Zhou 1 , A. Kumar 1 , H. T. Ravert 1 , J. Brasic 1 , W. Ye 1 , M. Alexander 1 , R. F. Dannals 1 , Jeffrey Galecki 1 , C. G. Lyketsos 1 , D. Skovronsky 2 , M. Pontecorvo 2 , Dean F. Wong 1 , 1 Johns Hopkins University, Baltimore, MD, USA; 2 AVID Pharmaceuticals, Philadelphia, PA, USA. Contact e-mail: prosenb9@jhmi.edu Background: There is growing research and clinical need for in vivo quantification of amyloid in Alzheimer’s disease (AD) for diagnosis and assessment of treatment response, but to date there is no 18 F ligand for PET imaging of amyloid-containing plaques. We present pilot results of such a radioligand [ 18 F] AV-45 in AD. Methods: Dynamic PET was performed on GE Advance. Regional brain distribution volume ratios (DVRs) were calculated. Cognition was measured with the Mini-Mental State Exam (MMSE), Wechsler Logical Memory-Delayed Recall (WMS), category fluency, and ADAS-Cog. Students’ t-test was used to compare group means and multivariate linear regression to examine correlations between cognitive and imaging variables, with p.05 as a test of statistical signif- icance. Results: AD patients (N=7) were younger than healthy controls (HC) (N=5) (mean 72 yrs. vs. 83 yrs) with less education (mean 17 years T300 Poster Presentations P1