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Trends Neurosci. 2015 Nov;38(11):674-681. doi: 10.1016/j.tins.2015.08.008.

Innate Immunity Fights Alzheimer's Disease.

Author information

1
Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, 1501 San Pablo Street, Room 337, Los Angeles, CA 90089-2821, USA.
2
Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, 1501 San Pablo Street, Room 337, Los Angeles, CA 90089-2821, USA. Electronic address: ttown@usc.edu.

Abstract

Alzheimer's disease (AD) is the most common age-related dementia. Pathognomonic accumulation of cerebral β-amyloid plaques likely results from imbalanced production and removal of amyloid-β (Aβ) peptides. In AD, innate immune cells lose their ability to restrict cerebral Aβ accumulation. At least in principle, mononuclear phagocytes can be enlisted to clear Aβ/β-amyloid from the brain. While the classical focus has been on dampening neuroinflammation in the context of AD, we hypothesize that rebalancing cerebral innate immunity by inhibiting actions of key anti-inflammatory cytokines returns the brain to a physiological state. Recent experiments demonstrating beneficial effects of blocking anti-inflammatory cytokine signaling in preclinical mouse models provide supportive evidence. This concept represents an important step toward innate immune-targeted therapy to combat AD.

KEYWORDS:

amyloid; apolipoprotein E; immunotherapy; interleukin-10; microglia; phagocytosis

PMID:
26549882
PMCID:
PMC4641041
DOI:
10.1016/j.tins.2015.08.008
[Indexed for MEDLINE]
Free PMC Article

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