No abstract

A heightened production of interleukin l/7 (IL-lb) has been reported in microglial-associated amyloid deposits in Alzheimer's disease (AD) brains. These plaques are composed predominantly of pIA4 peptide derived from B-amyloid precursor protein QAPP). We demonstrate that short-term (1 h) IL-l/3-treatment increases /3APPs secretion and concomitantly decreases cell-associated BAPP in human H4 neuroglioma cells. Long-term (5 h) IL-1s treatment did not alter secreted or cell-associated BAPP content. In contrast, the secretion of BIACcontaining epitope was not affected by short-term IL-l/3 stimulation; however, long-term IL-1s treatment decreased the amount of /?/A4-containing epitope secreted from the cells. These results show that IL-l/3 modifies the processing and secretion of j?APP to exacerbate perhaps the neuropathology of AD.

The HLA‐A, ‐B, ‐C, ‐DR, Bf and GLO phenotypes of 109 unrelated Saudi Arab males have been determined. HLA‐A and ‐B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations. Most similarities in antigen frequencies were seen between Saudi Arab and Iraqi populations. A high frequency of Bw50 was observed in Saudi Arabs. The frequencies of HLA‐DR antigens in Saudi Arabs were compared to European Caucasoids. HLA‐DR7 was at high frequency in Saudi Arabs. Linkage disequilibria between alleles of HLA loci was examined. Many instances of previously reported antigen associations were seen in Saudi Arabs, together with a number of associations which have not been described elsewhere. HLA‐Cw6‐Bw50‐DR7‐BfS0.7 is suggested as being a common haplotype in Saudi Arabs.

We have studied the activation of human ml-muscarinic receptors in a genetically engineered Chinese hamster ovary cell line (CHO-ml) to determine which second messenger systems affect the secretion of APP via the non-amyloidogenic route. Carbachol activation of the signaling pathways in CHO-ml cells promotes APP secretion by activation of both protein kinase C (PKC)-dependent or Ca(++)-dependent second messenger pathways. Both pathways converge to increase the enzyme activity of phospholipase A2 (PLA2), the enzyme that releases arachidonic acid from cellular stores. Directly activating PLA2 with melittin, a peptide from bee venom, or by adding arachidonic acid directly to cultured cells increases the secretion of APP. Thus, our results indicate that arachidonic acid is yet another cellular second messenger involved in regulating the metabolism of APP in addition to PKC and cytoplasmic Ca++. Moreover, activation of PLA2 appears to be an obligatory event in increasing the secretion of APP from CHO-ml cells by the various methods of activation that we have tried thus far.