Presenilin 2 mutations alter cystatin C trafficking in mouse primary neurons

Roberta Ghidoni, Luisa Benussi, Anna Paterlini, Cristina Missale, Alessia Usardi, Rossana Rossi, Laura Barbiero, PierFranco Spano, Giuliano Binetti

Research output: Contribution to journalArticlepeer-review


Mutations in the presenilin genes account for the majority of familial Alzheimer disease (FAD) cases. In the present report we demonstrated that the FAD-linked presenilin 2 mutations (PS2 M239I and T122R) alter cystatin C trafficking in mouse primary neurons reducing secretion of its glycosylated form. These mutations showed a different impact on cystatin C: PS2 T122R had a much stronger effect determining a dramatic intracellular accumulation of cystatin C (native and glycosylated), followed by a reduction in the secretion of both forms. Several experimental evidences suggest that cystatin C exerts a protective role in the brain and favors stem cells proliferation. Confocal imaging showed that the effect of PS2 T122R mutation was a massive recruitment of cystatin C into the neuronal processes, in the presence of an intact cytoskeletal structure. The consequent reduction in the cystatin C extracellular levels might result in a failure of neuroregeneration. Understanding the interplay of PS2 and cystatin C in the pathogenesis of AD might highlight new therapeutic prospective.

Original languageEnglish
Pages (from-to)371-376
Number of pages6
JournalNeurobiology of Aging
Issue number3
Publication statusPublished - Mar 2007


  • Cysteine protease
  • Familial Alzheimer disease
  • Glycosylated cystatin C
  • Mutation
  • Presenilin 2
  • Protein secretion

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)


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