Secretory leukocyte protease inhibitor protein regulates the penetrance of frontotemporal lobar degeneration in progranulin mutation carriers

Roberta Ghidoni, Rosa Flocco, Anna Paterlini, Michela Glionna, Loredana Caruana, Elisa Tonoli, Giuliano Binetti, Luisa Benussi

Research output: Contribution to journalArticle

Abstract

The discovery that mutations in the gene encoding for progranulin (GRN) cause frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases leading to dementia has brought renewed interest in progranulin and its functions in the central nervous system. Full length progranulin is preserved from cleavage by secretory leukocyte protease inhibitor (SLPI), one of the smallest serine protease inhibitor circulating in plasma. Herein, we investigated the relationship between circulating SLPI and progranulin in affected and unaffected subjects belonging to 26 Italian pedigrees carrying GRN null mutations. In GRN null mutation carriers, we demonstrated: i) an increase of circulating SLPI levels in affected subjects; ii) an age-related upregulation of the serine-protease inhibitor in response to lifetime progranulin shortage; and iii) a delay in the age of onset in subjects with the highest SLPI protein levels. The study of SLPI and its relation to progranulin suggests the existence of unexpected molecular players in progranulin-associated neurodegeneration.

Original languageEnglish
Pages (from-to)533-539
Number of pages7
JournalJournal of Alzheimer's Disease
Volume38
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • Frontotemporal dementia
  • GRN
  • Kaplan-Meier Survival curves
  • mutation
  • pedigrees
  • plasma
  • progranulin
  • SLPI protein

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Fingerprint Dive into the research topics of 'Secretory leukocyte protease inhibitor protein regulates the penetrance of frontotemporal lobar degeneration in progranulin mutation carriers'. Together they form a unique fingerprint.

  • Cite this