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

Neurosci Lett. 2003 Mar 27;339(3):183-6. doi: 10.1016/s0304-3940(03)00030-2.


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-amyloid 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / physiology*
  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Astrocytes / enzymology*
  • Brain / enzymology
  • Down-Regulation / physiology
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neprilysin / genetics
  • Neprilysin / metabolism*
  • Plaque, Amyloid / enzymology*
  • Plaque, Amyloid / genetics
  • Up-Regulation / physiology


  • Amyloid beta-Peptides
  • Neprilysin