1. The Role of Alternative Activation in Microglia
Rachel Suppok, Tara Sweet, Ph.D., John A. Olschowka, Ph.D., Kerry O’Banion, M.D., Ph.D.
(2015)
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and
Dentistry
Abstract
Alzheimer’s disease is the most prevalent form of dementia in the U.S. today, with as
many as 5.1 million Americans suffering from the disorder, according to the National Institute on
Aging. One of the characteristic features of this neurodegenerative disease is extracellular
deposition of the peptide amyloid β (Aβ), which form neuritic plaques in the central nervous
system (CNS). Aβ has proinflammatory effects in the CNS, and the inflammatory cascade
hypothesis of Alzheimer’s disease suggests that Aβ deposition drives neuroinflammation, which
in turn leads to the creation of more Aβ plaques. The microglia around the plaques produce
elevated amounts of inflammatory factors, but the microglia also play an important role in the
phagocytosis and degradation of Aβ.
Treatment with interleukin-4 (IL-4) has been proposed to mitigate the pathology of
Alzheimer’s disease by enhancing Aβ phagocytosis. IL-4 induces a transition to the alternative
activation (M2) phenotype of microglia. Alternatively activated myeloid cells, including
microglia, contribute to anti-inflammatory functions and tissue repair by releasing anti-
inflammatory cytokines, displaying enhanced phagocytosis, and secreting growth factors.
Meanwhile, irradiation increases the plaque burden.
In order to better understand the role of IL-4 and its potential for treatment in
Alzheimer’s disease, we devised two experiments. First, we examined whether IL-4 drives cell
proliferation by counting the number of BrdU+ cells in the brains of mice that had been injected

2. with either IL-4 or saline, as BrdU+ marks dividing cells. For our second experiment, we wanted
to investigate whether radiation would affect the IL-4-induced phenotypic shift towards
alternative activation. Therefore, we injected both irradiated and un-irradiated mice with IL-4
and performed an IHC for arginase 1, a marker of alternatively activated myeloid cells.
For the first experiment, we found no significant difference between proliferation in IL-4-
injected tissue and saline-injected tissue. In the second experiment, the location of the injection
site precluded any relevant data.