The current development of immunotherapy for Alzheimer's disease is based on the assumption that human-derived amyloid ␤ protein (A␤) can be targeted in a similar manner to animal cell-derived or synthetic A␤. Because the structure of A␤ depends on its source and the presence of cofactors, it is of great interest to determine whether human-derived oligomeric A␤ species impair brain function and, if so, whether or not their disruptive effects can be prevented using antibodies. We report that untreated ex vivo human CSF that contains A␤ dimers rapidly inhibits hippocampal long-term potentiation in vivo and that acute systemic infusion of an anti-A␤ monoclonal antibody can prevent this disruption of synaptic plasticity. A␤ monomer isolated from human CSF did not affect long-term potentiation. These results strongly support a strategy of passive immunization against soluble A␤ oligomers in early Alzheimer's disease.

Complement factor C3 is the central component of the complement system and a key inflammatory protein activated in Alzheimer's disease (AD). Previous studies demonstrated that inhibition of C3 by overexpression of sCrry in an AD mouse model led to reduced microgliosis, increased Aβ plaque burden and neurodegeneration. To further address the role of C3 in AD pathology, we generated a complement C3-deficient APP transgenic AD mouse model (APP;C3 −/− ). Brains were analyzed at 8, 12 and 17 months of age by immunohistochemical and biochemical methods and compared with age-matched APP transgenic mice. At younger ages (8-12 months), no significant neuropathological differences were observed between the two transgenic lines. In contrast, at 17 months of age, APP;C3 −/− mice showed significant changes of up to two-fold increased total amyloid-beta (Aβ) and fibrillar amyloid plaque burden in midfrontal cortex and hippocampus which correlated with: a) significantly increased TBS-insoluble Aβ42 levels and reduced TBS-soluble Aβ42 and Aβ40 levels in brain homogenates, b) a trend for increased Aβ levels in the plasma, c) a significant loss of NeuN-positive neurons in the hippocampus, and d) differential activation of microglia towards a more alternative phenotype (e.g., significantly increased CD45-positive microglia, increased brain levels of IL-4 and IL-10, and reduced levels of CD68, F4/80, iNOS and TNF). Our results suggest a beneficial role for complement C3 in plaque clearance and neuronal health as well as in modulation of the microglia phenotype.

Background and Purpose-Endovascular treatment has increasingly been used for aneurismal subarachnoid aneurismal hemorrhage. The aim of this analysis is to assess the current evidence regarding safety and efficiency of clipping compared with coiling. Methods-We conducted a meta-analysis of studies that compared clipping with coiling between January 1999 and July 2012. Comparison of binary outcomes between treatment groups was described using odds ratios (OR; clip versus coil). Results-Four

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