S3‐01‐04: THERAPEUTIC STRATEGIES: APOE IN TRAUMATIC BRAIN INJURY

not available. S3-01-02 APOE AND ALZHEIMER’S DISEASE IMAGING BIOMARKERS Beth C. Mormino, Massachusetts General Hospital, Boston, MA, USA. Contact e-mail: bmormino@stanford.edu Abstract not available.not available. S3-01-03 APOE AND SEX DIFFERENCES ON ALZHEIMER’S DISEASE RISK Arthur W. Toga, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Contact e-mail: toga@loni.usc.edu Abstract not available.not available. S3-01-04 THERAPEUTIC STRATEGIES: APOE IN TRAUMATIC BRAIN INJURY Cheryl Wellington, University of British Columbia, Vancouver, BC, Canada. Contact e-mail: cheryl.wellington@ubc.ca Abstract not available.not available. SYMPOSIA S3-02 MECHANISMS OF NEURONAL DEATH S3-02-01 NECROPTOSIS ACTIVATION IN ALZHEIMER’S DISEASE Antonella Caccamo, Caterina Branca, Salvatore Oddo, Arizona StateUniversity, Tempe,AZ,USA.Contact e-mail: caccamo@asu.edu Background: Neuronal loss is a major pathological feature of Alzheimer’s disease (AD). Nevertheless, the mechanisms underlying this key event in the disease pathogenesis are not clear. Methods:Necroptosis, a programmed form of necrosis, is performed by the mixed lineage kinase domain-like (MLKL) protein, which is activated by receptor-interactive protein kinases (RIPK) 1 and 3. Necroptosis is activated in various neurodegenerative disorders including multiple sclerosis and amyotrophic lateral sclerosis. However, it remains to be determined whether necroptosis plays a role in AD. Results:We show that necroptosis is activated in human AD brains and its activation correlates with brain weight and cognitive scores. We also show that necroposis is also activated in 5xFAD mice, which are characterized by marked neuronal loss. Using complementary in vitro and in vivo approaches, we found that reducing necroptosis activation rescues AD-related neuronal loss. Conclusions: Overall, these data provide the first direct evidence that necroptosis is a mechanism involved in neurodegeneration in AD. S3-02-02 STRESS GRANULE FORMATION AND NEURONAL DEATH Ben Wolozin, Boston University School of Medicine, Boston, MA, USA. Contact e-mail: bwolozin@bu.edu Abstract not available.not available. S3-02-03 NEUROINFLAMMATORY PROCESSES AND NEURODEGENERATION Roisin M. McManus, Michael T. Heneka, German Center for Neurodegenerative Diseases, Bonn, Germany. Contact e-mail: roisin. mcmanus@dzne.de Abstract not available.not available. S3-02-04 MICROGLIAL ACTIVATION IN NEURODEGENERATIVE DISEASES: OPPORTUNITIES FOR THERAPEUTIC INTERVENTION Diego Gomez-Nicola, University of Southampton, Southampton, United Kingdom. Contact e-mail: d.gomez-nicola@soton.ac.uk Background:Microglial cells are the resident immune cells of the brain andplay crucial roles in the regulation of normal andpathological neural functions. Our lab aims at studying the balance of the numbers of microglial cells from development to ageing, to better understand the roles of these cells in the brain, through a multidisciplinary approach using invivomodels, geneticmolecular tools and behavioural analysis of brain function. We aim to define how microglial cells control their numbers and phenotype during not only healthy ageing, but also disease. Microglial cells play a key role in the development and maintenance of the inflammatory response characteristic of several neurodegenerative disorders, showing enhanced proliferation and morphological activation. Methods:We are using a multidisciplinary approach combining the study of laboratory models of chronic neurodegeneration, including prion disease, Alzheimer’s disease (AD) and ALS,with the study of post-mortem samples from patients, to describe the time-course and regulation of microglial proliferation.Results:Our results demonstrate thatmicroglial proliferation is an important feature of the evolution of chronic neurodegenerative disease, with direct implications for understanding the contribution of the CNS innate immune response to disease progression. We have shown that the control of microglial numbers in prion, AD and ALS is regulated by the activation of the Colony Stimulating Factor 1 Receptor (CSF1R). Conclusions: Pharmacological inhibition of CSF1R leads to a diminished proliferation of microglia and the amelioration of the behavioural and neuropathological symptoms of chronic neurodegeneration. FEATURED RESEARCH SESSIONS F3-01 PERIOPERATIVE NEUROCOGNITIVE DISORDERS AND VASCULAR RISK F3-01-01 POSTOPERATIVE CHANGES IN CSF BIOMARKERS AND RESTING-STATE FUNCTIONAL NEUROIMAGING SIGNAL CHARACTERISTICS Jeffrey Browndyke, Mary Cooter, Joseph P. Mathew, Miles Berger and MADCO-PC Investigators, Duke University Medical Center, Durham, NC, USA; Duke Brain Imaging & Analysis Center, Durham, NC, USA; Duke Institute for Brain Sciences, Durham, NC, USA. Contact e-mail: j.browndyke@duke.edu