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Cytokines in Alzheimer pathogenesis
Author(s) -
Griffin Sue T.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.404.3
Subject(s) - microglia , neurite , senile plaques , pathogenesis , alzheimer's disease , neuroscience , cytokine , neuroinflammation , biology , disease , medicine , immunology , pathology , inflammation , in vitro , genetics
Our discovery that overexpression of cytokines such as interleukin‐1 (IL‐1) and S100B accompanies the glial activation, noted by Alzheimer himself, led to our proposed cytokine hypothesis to explain the progressive nature of the clinical and neuropathological changes of Alzheimer's disease (AD). This hypothesis states that in response to neuronal insults of known and unknown origin, e.g., genetic inheritance and environmental factors, microglia and astrocytes are activated and release excess IL‐1 and S100B, respectively. As these glial events occur in fetuses and neonates with Down's syndrome (DS) decades before the inevitable neuropathological changes of AD in DS, glial changes must precede rather than follow AD‐related neuropathologies such as the neuritic Abeta plaques diagnostic of AD. As IL‐1 induces neuronal expression of Abeta precursor protein (APP) and astrocytic expression of S100B in vivo, the excess IL‐1 and S100B in AD and DS likely act as drivers of Abeta deposition and dystrophic neurite proliferation necessary for formation of neuritic Abeta plaques. In this way chronic excesses of IL‐1 and S100B stress neurons to relentless production of APP and nonsensical neurite growth, creating a cycle of neuronal dysfunction and loss and further glial activation and cytokine overexpression. Support: NIA AG12411 and the Donald W. Reynolds Foundation