Increased levels of the Kunitz protease inhibitor-containing βAPP mRNAs in rat brain following neurotoxic damage

Abstract

Deposits of β-amyloid are one of the main pathological characteristics of Alzheimer's disease. The β-amyloid peptide (or β/A4) constituent of these deposits is derived from the β-amyloid precursor protein (βAPP), which is expressed in several isoforms. It has been suggested that an imbalance in the normal ratio between the Kunitz protease inhibitor (KPI)-containing βAPPs versus the non containing forms could result in altered processing of βAPP and progressive β/A4 deposition. We have studied the expression of four βAPP isoforms in the rat brain after intracerebroventricular application of kainic acid. Increased levels of the KPI-containing βAPP and GFAP mRNAs were observed in tissues surrounding areas of neuronal damage. A parallel increase of βAPP and GFAP immunoreactivity was observed in reactive astrocytes in these areas. These results suggest that the normal ratio of βAPP isoforms may be profoundly altered as a result of neuronal damage and that non-neuronal cells may respond to neuronal injury by increased expression of the KPI-containing βAPP isoforms.