PMID- 26021560
OWN - NLM
STAT- MEDLINE
DCOM- 20160607
LR  - 20181202
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 49
DP  - 2015 Oct
TI  - Inflammatory molecules in Frontotemporal Dementia: cerebrospinal fluid signature 
      of progranulin mutation carriers.
PG  - 182-7
LID - S0889-1591(15)00132-4 [pii]
LID - 10.1016/j.bbi.2015.05.006 [doi]
AB  - 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+/-49pg/ml; P⩽0.05). In GRN mutation carriers versus controls, CSF levels of 
      MCP-1 were unchanged, whereas Interferon-gamma-inducible protein-10 (IP-10) levels 
      were increased (809.17+/-240.0 versus 436.61+/-202.5pg/ml; P=0.012). In the same 
      group, TNFalpha 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+/-70pg/ml, 
      respectively; P<0.05). Moreover, IP-10, IL-15 and RANTES CSF levels were not 
      influenced by age, whereas MCP-1 levels increased with age (rho=0.48; P=0.007). In 
      conclusion, inflammatory de-regulation was observed in both sporadic FTLD and GRN 
      carriers compared to controls, with a specific inflammatory profile for the 
      latter group.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Galimberti, D
AU  - Galimberti D
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy. Electronic address: daniela.galimberti@unimi.it.
FAU - Bonsi, R
AU  - Bonsi R
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Fenoglio, C
AU  - Fenoglio C
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Serpente, M
AU  - Serpente M
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Cioffi, S M G
AU  - Cioffi SM
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Fumagalli, G
AU  - Fumagalli G
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Arighi, A
AU  - Arighi A
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Ghezzi, L
AU  - Ghezzi L
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Arcaro, M
AU  - Arcaro M
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Mercurio, M
AU  - Mercurio M
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Rotondo, E
AU  - Rotondo E
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
FAU - Scarpini, E
AU  - Scarpini E
AD  - Department of Pathophysiology and Transplantation, University of Milan, 
      Fondazione Ca Granda, IRCCS Ospedale Maggiore Policlinico, Via F. Sforza 35, 
      20122 Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150527
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (GRN protein, human)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-15)
RN  - 0 (Progranulins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Aged
MH  - Chemokine CCL2/blood/cerebrospinal fluid
MH  - Chemokine CXCL10/blood/cerebrospinal fluid
MH  - Female
MH  - Frontotemporal Dementia/*cerebrospinal fluid/complications/*genetics
MH  - Humans
MH  - Inflammation/*cerebrospinal fluid/complications/*genetics
MH  - Inflammation Mediators/blood/*cerebrospinal fluid
MH  - Intercellular Signaling Peptides and Proteins/*genetics
MH  - Interleukin-15/blood/cerebrospinal fluid
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Progranulins
MH  - Tumor Necrosis Factor-alpha/blood/cerebrospinal fluid
OTO - NOTNLM
OT  - Cerebrospinal fluid
OT  - Chemokines
OT  - Cytokines
OT  - Frontotemporal Dementia (FTD)
OT  - Frontotemporal Lobar Degeneration (FTLD)
OT  - Inflammation
OT  - Pick dementia
OT  - Progranulin (GRN)
EDAT- 2015/05/30 06:00
MHDA- 2016/06/09 06:00
CRDT- 2015/05/30 06:00
PHST- 2015/02/09 00:00 [received]
PHST- 2015/04/30 00:00 [revised]
PHST- 2015/05/19 00:00 [accepted]
PHST- 2015/05/30 06:00 [entrez]
PHST- 2015/05/30 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
AID - S0889-1591(15)00132-4 [pii]
AID - 10.1016/j.bbi.2015.05.006 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2015 Oct;49:182-7. doi: 10.1016/j.bbi.2015.05.006. Epub 2015 
      May 27.