There is ample genetic, biochemical, cellular and molecular evidence to show that the amyloid β peptide (Aβ), 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 α1-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 Aβ 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 Aβ clearance. The main objective of this review is to summarize the role of astrocytosis and ACT in the pathogenesis of AD.