Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis

Romana Höftberger, Stephanie Fink, Fahmy Aboul-Enein, Gergö Botond, J. Oláh, T. Berki, J. Ovádi, Hans Lassmann, Herbert Budka, Gabor G. Kovacs

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/ p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, a-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.

Original languageEnglish
Pages (from-to)1847-1857
Number of pages11
JournalGLIA
Volume58
Issue number15
DOIs
Publication statusPublished - Nov 15 2010

Fingerprint

Oligodendroglia
Tubulin
Polymerization
Multiple Sclerosis
Proteins
Inclusion Bodies
Cytoplasm
Synucleins
Chronic Progressive Multiple Sclerosis
Multiple System Atrophy
Relapsing-Remitting Multiple Sclerosis
Demyelinating Diseases
Myelin Sheath
Ubiquitin
Autopsy
Up-Regulation
Central Nervous System

Keywords

  • Degeneration
  • Multiple sclerosis
  • Oligodendrocyte
  • Remyelination
  • Tubulin polymerization promoting protein (TPPP/ p25)

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis. / Höftberger, Romana; Fink, Stephanie; Aboul-Enein, Fahmy; Botond, Gergö; Oláh, J.; Berki, T.; Ovádi, J.; Lassmann, Hans; Budka, Herbert; Kovacs, Gabor G.

In: GLIA, Vol. 58, No. 15, 15.11.2010, p. 1847-1857.

Research output: Contribution to journalArticle

Höftberger, R, Fink, S, Aboul-Enein, F, Botond, G, Oláh, J, Berki, T, Ovádi, J, Lassmann, H, Budka, H & Kovacs, GG 2010, 'Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis', GLIA, vol. 58, no. 15, pp. 1847-1857. https://doi.org/10.1002/glia.21054
Höftberger, Romana ; Fink, Stephanie ; Aboul-Enein, Fahmy ; Botond, Gergö ; Oláh, J. ; Berki, T. ; Ovádi, J. ; Lassmann, Hans ; Budka, Herbert ; Kovacs, Gabor G. / Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis. In: GLIA. 2010 ; Vol. 58, No. 15. pp. 1847-1857.
@article{713aee36dd40483283f0a9b5a134e07c,
title = "Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis",
abstract = "Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/ p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, a-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.",
keywords = "Degeneration, Multiple sclerosis, Oligodendrocyte, Remyelination, Tubulin polymerization promoting protein (TPPP/ p25)",
author = "Romana H{\"o}ftberger and Stephanie Fink and Fahmy Aboul-Enein and Gerg{\"o} Botond and J. Ol{\'a}h and T. Berki and J. Ov{\'a}di and Hans Lassmann and Herbert Budka and Kovacs, {Gabor G.}",
year = "2010",
month = "11",
day = "15",
doi = "10.1002/glia.21054",
language = "English",
volume = "58",
pages = "1847--1857",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "15",

}

TY - JOUR

T1 - Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis

AU - Höftberger, Romana

AU - Fink, Stephanie

AU - Aboul-Enein, Fahmy

AU - Botond, Gergö

AU - Oláh, J.

AU - Berki, T.

AU - Ovádi, J.

AU - Lassmann, Hans

AU - Budka, Herbert

AU - Kovacs, Gabor G.

PY - 2010/11/15

Y1 - 2010/11/15

N2 - Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/ p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, a-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.

AB - Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/ p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, a-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.

KW - Degeneration

KW - Multiple sclerosis

KW - Oligodendrocyte

KW - Remyelination

KW - Tubulin polymerization promoting protein (TPPP/ p25)

UR - http://www.scopus.com/inward/record.url?scp=78649351587&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649351587&partnerID=8YFLogxK

U2 - 10.1002/glia.21054

DO - 10.1002/glia.21054

M3 - Article

C2 - 20737479

AN - SCOPUS:78649351587

VL - 58

SP - 1847

EP - 1857

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 15

ER -