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Current Alzheimer Research
ISSN (Print): 1567-2050
ISSN (Online): 1875-5828
VOLUME: 8
ISSUE: 2
DOI: 10.2174/156720511795256017      Price:  $58









How to Get from Here to There: Macrophage Recruitment in Alzheimers Disease

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Author(s): K. Rezai-Zadeh, D. Gate, G. Gowing and T. Town
Pages 156-163 (8)
Abstract:
Alzheimers disease (AD) is pathologically defined by presence of intracellular neurofibrillary tangles and extracellular amyloid plaques comprised of amyoid-β (Aβ) peptides. Despite local recruitment of brain microglia to sites of amyloid deposition, these mononuclear phagocytes ultimately fail at restricting β-amyloid plaque formation. On the other hand, it is becoming increasingly clear that professional phagocytes from the periphery possess Aβ clearance aptitude. Yet, in order to harness this beneficial innate immune response, effective strategies must be developed to coax monocytes/ macrophages from the periphery into the brain. It has previously been suggested that Aβ ‘immunotherapy’ clears cerebral Aβ deposits via mononuclear phagocytes, and recent evidence suggests that targeting transforming growth factor- β-Smad 2/3 signaling and chemokine pathways such as Ccr2 impacts blood-to-brain trafficking of these cells in transgenic mouse models of AD. It has also been shown that the fractalkine receptor (Cx3cr1) pathway plays a critical role in chemotaxis of mononuclear phagocytes toward neurons destined for death in AD model mice. In order to translate these basic science findings into AD treatments, a key challenge will be to develop a new generation of pharmacotherapeutics that safely and effectively promote recruitment of peripheral amyloid phagocytes into the AD brain.
Keywords:
Mononuclear phagocyte, neurodegeneration, amyloid, Abeta, monocyte
Affiliation:
Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Steven Spielberg Building, Room 361, Los Angeles, CA 90048, USA.