Epidemiological evidence has demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) may lower the risk of developing Alzheimer's disease (AD). Cyclooxygenase (COX)-2, a target enzyme of NSAIDs which is involved in inflammatory reactions as well as physiological brain functions, has been found to be upregulated in AD brains. In the present study, we used immunohistochemistry to determine the localization and the cellular type of the COX-2-expressing cells as well as the spatial relationship between these cells and the characteristic β-amyloid (Aβ1–42)-immunopositive senile plaques (SP) or tau-positive neurofibrillary tangles (NFT) which are found in the brains of patients with a Presenilin-1 gene mutation. Numerous Aβ1–42-positive SP were detected throughout the brains. COX-2 immunoreactivity was present between SP mainly in pyramidal neurons in the cerebral cortex and the hippocampal formation. COX-2 was also found in small round cells in close association with SP. The COX-2-positive neurons were most dense in the superficial cortical layers, while tau-positive NFT were densest in the deeper layers. In the frontal and temporal cortices that were most severely affected COX-2-positive neurons were damaged and decreased in number. The COX-2 expression in these cells might contribute to Aβ accumulation or represent a cytoprotective reaction against the Aβ-related inflammatory process.
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