The role of phospholipase A2 in amyloid ?� uptake by microglia

Abstract

The accumulation of amyloid-beta (Abeta) is a key characteristic of Alzheimer's disease (AD). Microglia are the principle macrophages in the brain and are known to internalize Abeta, however the phagocytic function is impaired as AD progresses. Cytosolic phospholipase A2 (cPLA2) and calcium-independent PLA2 (iPLA2) are two major groups of PLA2s that are involved in modulating membrane properties, intracellular trafficking and the cellular inflammatory responses. Here, we study the role of cPLA2 and iPLA2 in the uptake of Abeta 1-42 by microglia in vitro. We found that the uptake of Abeta 1-42 was rapid (<15 minutes) and remained unchanged up to 60 minutes. Also, inhibition of cPLA2 greatly reduced Abeta 1-42 uptake while increasing cPLA2 activation did not affect Abeta 1-42 uptake. iPLA2 appears to reduce the rate of Abeta 1-42 uptake, but had no influence on the uptake level later on. Furthermore, cPLA2 and iPLA2 are not involved in intercellular processing of Abeta 1-42.