Cytosolic prostaglandin E synthase: expression patterns in control and Alzheimer's disease brains.

Anti-inflammatory drugs reduce the risk of Alzheimer's disease but fail to slow its progression. Studying the expression of prostaglandin E(2) synthases downstream of cyclooxygenase-2 is important. Here, the expression patterns of cytosolic prostaglandin E( 2) synthases, an immediate prostaglandin E(2) source was investigated. Sections taken from the middle frontal gyrus of brains of 10 patients with Alzheimer's and 5 age-matched controls were examined by immunostaining for the presence of the synthases. Immunofluorescence analysis of control brains showed that cytosolic prostaglandin E(2) synthases co-localize with microglia, neurons, and endothelium markers, but not with astrocytes or smooth muscle cells. Immunohistochemical staining for the synthases was positive in the pyramidal neurons of controls but barely detectable in the brain of Alzheimer's patients. These findings revealed that cytosolic prostaglandin E(2) synthases is found in microglia, neurons, and endothelium of control human middle frontal gyrus and that its levels decrease in pyramidal cells of Alzheimer's disease brains.

Elevated microsomal prostaglandin-E synthase-1 in Alzheimer's disease.

BACKGROUND: The proinflammatory prostaglandin E(2) (PGE(2)) fluctuates over time in the cerebrospinal fluid of patients with Alzheimer's disease (AD), but the cerebral distribution and expression patterns of microsomal prostaglandin-E synthase (mPGES)-1 have not been compared with those of normal human brains. METHODS: Middle frontal gyrus tissue from AD and age-matched control brains was analyzed by Western blot, immunofluorescence, and immunohistochemistry with mPGES-1-specific antibodies. RESULTS: Western blotting revealed that mPGES-1 expression was significantly elevated in AD tissue. Furthermore, immunofluorescence of mPGES-1 was observed in neurons, microglia, and endothelial cells of control and AD tissue. Although mPGES-1 was consistently present in astrocytes of control tissue, it was present in only some astrocytes of AD tissue. Immunohistochemical staining suggested that mPGES-1 was elevated in pyramidal neurons of AD tissue when compared with controls. CONCLUSIONS: The results suggest that mPGES-1 is normally expressed constitutively in human neurons, microglia, astrocytes, and endothelial cells but is up-regulated in AD.

Development of immunoassays for serum tartrate-resistant acid phosphatase isoform 5a.

BACKGROUND: Serum tartrate-resistant acid phosphatase (TRACP) consists of 2 structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a activity and protein. METHODS: Biotinylated anti-TRACP antibodies were used to immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl phosphate as substrate. TRACP 5a protein was measured with an independent peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for linearity of serum dose response, sensitivity and precision. Reference ranges for TRACP 5a were established from serum of 50 healthy males and 50 healthy age-matched females. Serum TRACP 5a activity and protein were determined in 29 cases of rheumatoid arthritis. RESULTS: Serum matrix interference in both TRACP 5a assays required dilution to 10% serum to approach linearity. Intra-assay and inter-assay CV% were <10%. Mean serum TRACP 5a activity and protein were significantly higher in healthy men than women. There was a slight, but significant age related increase in both serum TRACP 5a and 5b among females, but not males, from age 20 to 70 years. TRACP 5a activity was positively correlated to TRACP 5a protein in healthy sera. Neither TRACP 5a activity nor protein was correlated strongly to TRACP-5b activity. TRACP 5a protein was significantly increased in 8/29 RA sera, whereas TRACP 5a and 5b activities were not. TRACP 5a activity and protein were not significantly correlated in RA sera. CONCLUSIONS: Although TRACP 5a and 5b are related biosynthetically, their circulating levels in healthy humans were independent, suggesting differential regulation of expression. In chronic diseases, increased TRACP 5a may represent pathological processes of inflammation unrelated to bone metabolism.