Uncovering the role of astrocytes as scavenging cells in Alzheimer's Disease.
Accumulation of β-Amyloid (Aβ), the pathological hallmark of Alzheimer's disease (AD) is linked to neurodegeneration and cell death. It is hypothesized that imbalance between Aβ production and clearance causes Aβ accumulation and disease progression in sporadic AD. Furthermore, it was demonstrated that the common late- onset form of Alzheimer's disease is characterized by an overall impairment in Aβ clearance, positioning clearance mechanisms as highly relevant in AD research. Astrocytes, the most abundant cells in the brain, express a wide variety of phagocytic receptors and enzymes that may promote Aβ degradation and apoptotic cells removal, positioning them as major scavenging cells in the brain, in health and disease. We propose that persistent Aβ and apoptotic cells accumulation, despite astrocyte activation, may indicate that astrocyte clearance mechanisms are either overwhelmed or downregulated in AD. We use laser capture microdissection to selectively isolate near and far from plaque astrocytes and apply high-throughput sequencing to identify alterations in astrocytic gene expression. In addition, we propose that changes in Megf10, an astrocyte specific receptor involved in both Aβ and apoptotic cells clearance, may alter astrocytes' activation and functionality and exacerbate disease progression. Furthermore, to study the function of Megf10 as an engulfment receptor in-vivo we generated a Megf10 knockout mouse and characterize its pathology at the behavioral, cellular and molecular level. Thus, understanding the pathways by which astrocytes promote Aβ and apoptotic cells clearance may provide molecular targets for future therapeutic intervention in AD.
2015 Society for Neuroscience 45th Annual meeting. Chicago, USA. Poster presentation.
2015 XII European Meeting on Glial Cells in Health and Disease, Bilbao, Spain. Poster presentation.
2014 Glia in health and disease conference, Cold Spring Harbor Laboratories, USA. Poster presentation.
2014 Tel Aviv University Alzheimer’s Disease meeting, 22nd Annual Meeting. Tel Aviv, Israel. Oral presentation.
2013 Israeli Society for Neuroscience, 21nd Annual Meeting Eilat, Israel. Oral presentation.
2014 Clore scholarship for Outstanding PhD students.
2014 Dan David scholarship for Outstanding PhD students.
2013 TEVA fellowship for OutstandingPhD students in Neuroscience.
2009 Magna cum laudein B.Sc. Neuroscience Research Program,Tel Aviv University.
2007 Dean's list, The Faculty of Life Sciences, Tel Aviv University.
Research Categories: Behavioral Neuroscience, Cognitive neuroscience