Expression of invariant chain and pro-cathepsin L in Alzheimer's brain.

Inflammatory and immune systems are involved in the pathogenesis of Alzheimer's disease (AD), but those systems in the human brain have not been well identified. Cathepsin L might play a predominant role in the degradation of the invariant chain (Ii), which plays a critical role in antigen presentation to block the antigen-binding site of the major histocompatibility complex class II. We examined the expression of Ii and pro-cathepsin L (pCPL) in AD and normal brains by using immunohistochemistry. Ii expresses only in resting or mildly activated microglia, whereas pCPL strongly expresses in fully activated microglia but not in resting or mildly activated microglia in AD. Normal brain tissues have rarely been stained for Ii or pCPL. These results suggest that the activation of microglia leads to expression of a complex of Ii and human leukocyte antigen class II at first, and that further activation, which is followed by cluster formation and enlargement of microglia frequently seen in the AD brain, might cause pCPL expression to degrade Ii. Our study confirmed that microglia plays a central role in the immune system of the brain, and that an activation of microglia is involved in the pathogenesis of AD.