Inflammatory molecules in Frontotemporal Dementia: Cerebrospinal fluid signature of progranulin mutation carriers

D. Galimberti, R. Bonsi, C. Fenoglio, M. Serpente, S. M G Cioffi, G. Fumagalli, A. Arighi, L. Ghezzi, M. Arcaro, M. Mercurio, E. Rotondo, E. Scarpini

Research output: Contribution to journalArticlepeer-review

Abstract

Mutations in progranulin gene (. GRN) are one of the major causes of autosomal dominant Frontotemporal Lobar Degeneration (FTLD). Progranulin displays anti-inflammatory properties and is likely a ligand of Tumor Necrosis Factor (TNF) receptor 2, expressed on microglia. A few cytokines and chemokines are altered in cerebrospinal fluid (CSF) from patients with sporadic FTLD, whereas no information is available in familial cases. We evaluated, through BioPlex, levels of 27 inflammatory molecules, including cytokines, chemokines, and related receptors, in CSF and matched serum, from FTLD patients carrying GRN mutations as compared with sporadic FTLD with no GRN mutations and controls. Mean. ±. SD Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly increased in CSF from sporadic FTLD patients as compared with controls (334.27±151.5 versus 159.7±49. pg/ml; P≤0.05). In GRN mutation carriers versus controls, CSF levels of MCP-1 were unchanged, whereas Interferon-γ-inducible protein-10 (IP-10) levels were increased (809.17. ±240.0 versus 436.61±202.5. pg/ml; P=0.012). In the same group, TNFα and Interleukin (IL)-15 levels were decreased (3.18. ±1.41 versus 35.68±30.5pg/ml; P=0.013 and 9.34±5.54 versus 19.15±10.03pg/ml; P= 0.023, respectively). Conversely, Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) levels were decreased in patients, with or without mutations, as compared with controls (4.63±3.30 and 2.58±20 versus 87.57±70. pg/ml, respectively; P

Original languageEnglish
Pages (from-to)182-187
Number of pages6
JournalBrain, Behavior, and Immunity
Volume49
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • Cerebrospinal fluid
  • Chemokines
  • Cytokines
  • Frontotemporal Dementia (FTD)
  • Frontotemporal Lobar Degeneration (FTLD)
  • Inflammation
  • Pick dementia
  • Progranulin (GRN)

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

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