The CST3 B haplotype is associated with frontotemporal lobar degeneration

Eur J Neurol. 2010 Jan;17(1):143-6. doi: 10.1111/j.1468-1331.2009.02767.x. Epub 2009 Aug 5.


Background and purpose: Frontotemporal lobar degeneration (FTLD) is a common cause of early-onset dementia. Given the role of cystatin C in brain neurodegeneration and neuroregeneration, the aim of this study was to determine whether the cystatin C gene (CST3) was genetically associated with FTLD.

Methods: Hundred and eighty-six FTLD patients and 457 controls underwent CST3 analysis by PCR and KspI enzyme digestion.

Results: In FTLD patients negative for the presence of PGRN mutations, we found an over-representation of the CST3 haplotype B [odds ratio (OR = 1.619, P = 0.002)] and of AB/BB genotypes (OR = 1.704, P = 0.008) in FTLD patients.

Conclusions: The present study indicated the CST3 B haplotype as a putative risk factor for FTLD in PGRN mutations negative patients. The reduced level of cystatin C, previously associated with the B haplotype, might represent the molecular factor responsible for the increased risk. Long-term depletion of neurotrophic factors, such as cystatin C and progranulin proteins, seem to be a common theme in FTLD: boosting the expression of such proteins might be a promising therapeutic strategy for FTLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Cystatin C / genetics*
  • DNA Mutational Analysis
  • Female
  • Frontotemporal Lobar Degeneration / genetics*
  • Frontotemporal Lobar Degeneration / metabolism*
  • Frontotemporal Lobar Degeneration / physiopathology
  • Genetic Markers / genetics*
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Haplotypes / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Progranulins
  • Risk Factors


  • CST3 protein, human
  • Cystatin C
  • GRN protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Progranulins