Reactive astrocytes and α1-antichymotrypsin in Alzheimer's disease

There is ample genetic, biochemical, cellular and molecular evidence to show that the amyloid beta peptide (A beta), a proteolytic fragment of the amyloid precursor protein (APP), plays an important, if not causative role in Alzheimer's disease (AD). An additional hallmark of AD is the neuroinflammatory response that is associated with the amyloid deposition. We discovered that the acute phase protein alpha1-antichymotrypsin (ACT) is overexpressed by reactive astrocytes, and is tightly associated with virtually all amyloid plaques in the AD brain. It has also been shown that A beta and ACT bind in vitro. Recently, we have reported that astrocytic expression of ACT in APP transgenic mice leads to an increased plaque deposition in ACT/APP doubly transgenic mice compared to the APP mice alone, suggesting that ACT interferes with A beta clearance. The main objective of this review is to summarize the role of astrocytosis and ACT in the pathogenesis of AD. (C) 2001 Elsevier Science Inc. All rights reserved.