Interleukin- l/f? dissociates p-amyloid precursor protein and jhamyloid peptide secretion

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. Alzheimer's disease (AD) pathology is characterized by le- sions in brain regions important for intellectual function. The characteristic lesions of AD as well as Down's syndrome are amyloid depositions in the brain parenchyma in selected re- gions and in its vasculature. The amyloid deposits are com- posed predominantly of pIA4 peptide (l), derived from the transmembrane regions of B-amyloid precursor protein @APP) by proteolytic cleavage (2). The increased production of /I/A4 in some individuals leads to early onset of AD (3,4), implicating jIIA4 peptide as a pathogenic factor in AD.