Intravenous Infusion of Monocytes Isolated from 2-Week-Old Mice Enhances Clearance of Beta-Amyloid Plaques in an Alzheimer Mouse Model

Alzheimer's disease (AD) is characterized by the deposition of β-amyloid (Aβ) senile plaques and tau-associated neurofibrillary tangles. Other disease features include neuroinflammation and cholinergic neurodegeneration, indicating their possible importance in disease propagation. Recent studies have shown that monocytic cells can migrate into the AD brain toward Aβ plaques and reduce plaque burden. The purpose of this study was to evaluate whether the administration of intravenous infusions of 'young' CD11b-positive (+) monocytes into an AD mouse model can enhance Aβ plaque clearance and attenuate cognitive deficits. Peripheral monocytes were isolated from two-week-old wildtype mice using the Pluriselect CD11b+ isolation method and characterized by FACS analysis for surface marker expression and effective phagocytosis of 1 μm fluorescent microspheres, FITC-Dextran or FITC-Aβ1-42. The isolated monocytes were infused via the tail vein into a transgenic AD mouse model, which expresses the Swedish, Dutch/Iowa APP mutations (APPSwDI). The infusions began when animals reached 5 months of age, when little plaque deposition is apparent and were repeated again at 6 and 7 months of age. At 8 months of age, brains were analyzed for Aβ+ plaques, inflammatory processes and microglial (Iba1) activation. Our data show that infusions of two-week-old CD11b+ monocytes into adult APPSwDI mice results in a transient improvement of memory function, a reduction (30%) in Aβ plaque load and significantly in small (40 μm) plaques. In addition, we observe a reduction in Iba1+ cells, as well as no marked elevations in cytokine levels or other indicators of inflammation. Taken together, our findings indicate that young CD11b+ monocytes may serve as therapeutic candidates for improved Aβ clearance in AD

Evaluating knowledge exchange in interdisciplinary and multi-stakeholder research

Interdisciplinary and multi-stakeholder research is increasingly being promoted and implemented to enhance understanding of global environment change, identify holistic policy solutions, and assist implementation. These research activities are social processes aiming to enhance the exchange and translation of knowledge. Emphasis on the design and management of knowledge exchange is increasing, but learning about how to do this better is hampered by lack of conceptual development and appropriate methods to evaluate complex and multifaceted knowledge exchange processes. This paper therefore develops principles for the evaluation of knowledge exchange in interdisciplinary, multi-stakeholder environmental change research. The paper is based on an analysis of 135 peer-reviewed evaluations of knowledge exchange from diverse disciplines. The results indicate strong relationships between the field of study (e.g. health care, environmental management), the way knowledge and knowledge exchange were conceptualised and implemented, the approach used for the evaluation, and the outcomes being evaluated. A typology of seven knowledge exchange evaluations is presented to guide discussions about the underlying assumptions of different approaches to knowledge exchange and its evaluation. Five principles for knowledge exchange evaluation are also identified: (i) design for multiple end users; (ii) be explicit about why a particular approach to knowledge exchange is expected to deliver its outcomes; (iii) evaluate diverse outcomes; (iv) use evaluations as part of the process of delivering knowledge exchange; and (v) use mixed methods to evaluate knowledge exchange. We conclude that a catch-all approach to evaluation is neither appropriate nor desirable. Instead, approaches that focus on understanding the underlying processes of knowledge exchange, assess the relative contribution of other factors in shaping outcomes in addition to knowledge exchange, and that involve multiple stakeholders in implementing evaluations, will be the most appropriate for evaluating knowledge exchange in interdisciplinary global environmental change research. © 2014 Elsevier Ltd