[O1–02–05]: GENOTYPIC VARIANCE MAY EXPLAIN THE BALANCE OF EARLY CORTICAL VERSUS STRIATAL AMYLOID DEPOSITION IN AUTOSOMAL DOMINANT AD

dominant Alzheimer disease (ADAD). Methods: Non-mutation carriers (NC, n1⁄458, age1⁄440.669.7years) and mutation carriers (MC, n1⁄4108, age1⁄441.669.5years) underwent GRE MR sequences to detect MCH. All individuals had at least 2 imaging visits spaced by 1.961.1years. MCH number, siderosis, and macroscopic hemorrhages were visually quantified on each scan. Longitudinal analysis were performed to characterize the pattern of progression of MCHs with the mutation type, estimated year to symptom onset (EYO) for asymptomatic participants, and dementia using clinical dementia rating (CDR). Results: MCH were observed in 19 participants (11%), 18 of whom were MCs (PSEN11⁄413, PSEN21⁄41 and APP1⁄44). For all participants with MCH at baseline, the rate of increase per year was 0 for NCs and 0.8863.66 for MCs overall, but 7.0563.04 MCHs per year for 13 participants with 2 MCHs or more at baseline (mutation type was unassociated with rate of increase, (Figure 1).). In MCs, the increased rate per year was higher once past the estimated symptom onset (EYO>0, p<0.0005) and when they were cognitively impaired (CDR>0, p<0.005) (Figure 2). Siderosis was detected in participants with (n1⁄43) or without (n1⁄42) MCH. Macrohemorrhages were present only in 2 participants with MCHs within the APPmutation type and could not be directly correlated with the presence of MCHs. Conclusions: In individuals with ADAD, the presence of MCHs, even in very low numbers, convey a high risk of more MCHs at or beyond the EYO. An increase in MCHs over time accompanied or not by siderosis, or macroscopic hemorrhage may be part of the natural history of ADAD mutations. O1-02-05 GENOTYPIC VARIANCE MAY EXPLAIN THE BALANCE OF EARLY CORTICAL VERSUS STRIATAL AMYLOID DEPOSITION IN AUTOSOMAL DOMINANT AD Bernard J. Hanseeuw, Eric McDade, Aaron P. Schultz, Ralph N. Martins, Peter R. Schofield, Colin L. Masters, Neill R. Graff-Radford, Stephen Salloway, Adrian Danek, Johannes Levin, Virginia Buckles, Alison M. Goate, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, Keith Johnson, Reisa A. Sperling, Jasmeer P. Chhatwal, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston,MA, USA; Institute of Neuroscience, Universit e Catholique de Louvain, Brussels, Belgium; Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; Washington University School of Medicine, St. Louis, MO, USA; Massachusetts General Hospital, Charlestown, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA; School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, Australia; Australian Alzheimer’s Research Foundation, Perth, Australia; Neuroscience Research Australia and University of New South Wales, Sydney, Australia; The University of Melbourne, Parkville, Australia; The Florey Institute of Neuroscience and Mental Health, Parkville, Australia; Mayo Clinic, Jacksonville, FL, USA; Alpert Medical School of Brown University, Providence, RI, USA; Department of Neurology, LMU Munich, Munich, Germany; University of Munich, Munich, Germany; Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Massachusetts General Hospital and the Athinoula A Martinos Center for Biomedical Imaging, Boston, MA, USA. Contact e-mail: jchhatwal@partners.org