Inflammatory reaction in experimental autoimmune encephalomyelitis (EAE) is accompanied by a microglial expression of the beta A4-amyloid precursor protein (APP).
Neuropathological studies of the amyloid depositions and senile plaques in the brains of elderly patients or patients diagnosed with Alzheimer's disease reveal the conspicuous presence of numerous proteins which are usually expressed during reactions of the immune system. This has led to speculations that the pathomechanism of neurodegenerative diseases might involve inflammatory processes. These considerations constitute the theoretical basis for therapeutic intervention with antiinflammatory drugs in neurodegenerative diseases. Here, we show that the beta A4-amyloid precursor (APP) is rapidly induced in microglia in a model of experimental autoimmune encephalomyelitis (EAE). Using specific monoclonal antibodies against APP, the first glial cells newly expressing APP immunoreactivity were found at an early preclinical stage, i.e., 24 h after T-cell transfer. At the peak of clinical disease (6 days after T-cell transfer), numerous characteristically ramified cells were strongly positive for APP. Based on morphology and double-labeling, most of the de novo APP-expressing cells were identified as microglia. Additionally, APP-immunoreactive round cells were detected in and around perivascular infiltrates. Reflecting the course of the clinical disease, the induction of APP immunoreactivity terminated in the postclinical stage, i.e., 14 days after T-cell transfer. These results support earlier work demonstrating that microglia can rapidly de novo synthesise APP not only in response to direct nerve injury (Banati et al: Glia 9:199, 1993a) but also in immune-mediated disease. Apart from its possible therapeutic relevance, such a production of APP--reminiscent of an acute phase protein-suggests a role of APP in immune and repair mechanisms of the central nervous system.
Banati
R B
RB
Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, Germany.
Gehrmann
J
J
Lannes-Vieira
J
J
Wekerle
H
H
Kreutzberg
G W
GW
D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D017628:Microglia / Q000502:physiology*; D004676:Myelin Basic Protein / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014373:Tuberculin / Q000276:immunology
D016564:Amyloid beta-Protein Precursor; D004676:Myelin Basic Protein; D014373:Tuberculin