Aging-related down-regulation of neprilysin, a putative β-amyloid-degrading enzyme, in transgenic Tg2576 Alzheimer-like mouse brain is accompanied by an astroglial upregulation in the vicinity of β-amyloid plaques

Pathological accumulation of cortical beta-amyloid is an early and consistent feature of Alzheimer's disease. Brain level of beta-amyloid is determined both by its production and by its catabolism. Neprilysin, a zinc metalloproteinase has been suggested as potential candidate of beta-amyloid-degrading enzyme in vivo. To address the question whether pathological accumulation of beta-arnyloid peptides in transgenic Tg2576 mice with Alzheimer-like pathology may affect beta-amyloid catabolism, the expression of neprilysin was studied during postnatal maturation and aging. Neprilysin protein but mRNA levels decreased in mouse cerebral cortex with age (2-22 months), independently of transgene status. Immunocytochemistry revealed few neprilysin-positive dystrophic neurites around beta-amyloid plaques and an upregulation of neprilysin in plaque-surrounding reactive astrocytes which may suggest a role of plaque-mediated astrogliosis in beta-amyloid degradation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.