Title:Glia-Driven Neuroinflammation and Systemic Inflammation in Alzheimer’s Disease
Volume: 19
Issue: 7
Author(s): Sadayuki Hashioka*, Zhou Wu and Andis Klegeris*
Affiliation:
- Department of Psychiatry, Shimane University, 89-1 Enya-cho, Izumo, Shimane 693-8501,Japan
- Department of Biology, Faculty of Science, University of British Columbia Okanagan Campus, Kelowna, BC, V1V 1V7,Canada
Keywords:
Neurodegenerative diseases, microglia, astrocytes, neurotoxicity, systemic inflammation, neuroprotective drugs,
L-type calcium channel blockers.
Abstract: The neuroinflammatory hypothesis of Alzheimer’s disease (AD) was proposed more than
30 years ago. The involvement of the two main types of glial cells microglia and astrocytes, in neuroinflammation,
was suggested early on. In this review, we highlight that the exact contributions of
reactive glia to AD pathogenesis remain difficult to define, likely due to the heterogeneity of glia
populations and alterations in their activation states through the stages of AD progression. In the
case of microglia, it is becoming apparent that both beneficially and adversely activated cell populations
can be identified at various stages of AD, which could be selectively targeted to either limit
their damaging actions or enhance beneficial functions. In the case of astrocytes, less information is
available about potential subpopulations of reactive cells; it also remains elusive whether astrocytes
contribute to the neuropathology of AD by mainly gaining neurotoxic functions or losing their
ability to support neurons due to astrocyte damage. We identify L-type calcium channel blocker,
nimodipine, as a candidate drug for AD, which potentially targets both astrocytes and microglia. It
has already shown consistent beneficial effects in basic experimental and clinical studies. We also
highlight the recent evidence linking peripheral inflammation and neuroinflammation. Several
chronic systemic inflammatory diseases, such as obesity, type 2 diabetes mellitus, and periodontitis,
can cause immune priming or adverse activation of glia, thus exacerbating neuroinflammation and
increasing risk or facilitating the progression of AD. Therefore, reducing peripheral inflammation is
a potentially effective strategy for lowering AD prevalence.
