INCREASED LEVELS OF THE KUNITZ PROTEASE INHIBITOR-CONTAINING BETA-APP MESSENGER-RNAS IN RAT-BRAIN FOLLOWING NEUROTOXIC DAMAGE

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