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CAP37, an inflammatory mediator in Alzheimer's disease
Author(s) -
Pereira H. Anne,
Logan Sreemathi,
Beverly Kandice,
Lanis Jordi,
Hinsley Heather,
Fung KarMing,
Adesina Adekunle
Publication year - 2008
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.22.1_supplement.167.11
Subject(s) - microglia , pathology , senile plaques , biology , alzheimer's disease , neuroscience , medicine , inflammation , disease
CAP37 is an inflammatory mediator that plays a key role in innate immunity. Recently, we showed that CAP37 is present in the vasculature of patients with Alzheimer's disease (AD) and that it is a potent regulator of microglial functions. The objective of this study was to extend these observations to determine the role of CAP37 as an inflammatory mediator in AD. Tissue was obtained from temporal, parietal, midbrain, and hippocampus from 10 AD patients, patients diagnosed with Pick's disease, Diffuse Lewy Body Dementia with AD‐aging, vascular dementia with no AD pathology, and sex‐ and age‐matched controls. Immunohistochemistry showed that in addition to the previously observed endothelial expression of CAP37 in AD patients, CAP37 was expressed in hippocampal neurons including dentate gyrus as well as pyramidal neurons of regions CA1–4 and the subiculum. Tissues obtained from patients with other neurodegenerative diseases and age‐ and sex‐matched controls lacked staining for CAP37. In vitro studies demonstrated that CAP37 is expressed in a dose‐ and time‐dependent fashion in HCN‐1A neurons in response to beta‐amyloid peptide 1–40 and tumor necrosis factor‐alpha but not interleukin 1‐beta. These findings lead us to hypothesize that CAP37 induced in neurons in AD patients activates microglia resulting in the exacerbation of the inflammatory cascade leading to neuronal death. Support: Alzheimer's Association.