The brain-specific protein TPPP/p25 in pathological protein deposits of neurodegenerative diseases
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Immunohistochemical detection of protein components of pathological inclusions is widely used for neuropathological diagnosis of neurodegenerative disorders. However, different antibodies and antigen unmasking methods may account for variability between research studies and thus may affect diagnostic accuracy. Using two different antibodies raised against either a segment (184–200 aa) or the full length of human recombinant brain-specific tubulin polymerization promoting protein TPPP/p25, we immunohistochemically screened neurodegenerative disorders, both with and without pathological α-synuclein structures. We tested three different epitope unmasking methods, we applied laser confocal microscopy to evaluate double immunolabelling, and we compared the amount of structures exhibiting TPPP/p25 and α-synuclein immunoreactivity. We demonstrate that there are a variety of staining patterns depending on the epitope retrieval method and antibody used. The antibody raised against aa 184–200 segment of TPPP/p25 is better in immunolabelling the majority of α-synuclein immunopositive neuronal and glial pathological profiles detectable in Parkinson’s disease, diffuse Lewy-body disease, and multiple system atrophy, in addition to immunostaining some extracellular huntingtin immunoreactive structures, lipofuscin, and neuromelanin particles. In contrast, the one raised against the full-length human recombinant TPPP/p25 is more suitable to immunodetect normal oligodendrocytes. Exposition of the segment aa 184–200 of TPPP/p25 in the aggregates of pathological inclusions renders this antibody a reliable marker of all types of α-synucleinopathies and suggests a role for TPPP/p25 in the aggregation process of some neurodegenerative conditions.
KeywordsTPPP/p25 α-synuclein Multiple system atrophy Lewy-body Oligodendroglia Immunohistochemistry
We are grateful to Gerda Ricken and Helga Flicker for their technical assistance. This work was supported in part by EU Grant FP6, BNEII No LSHM-CT-2004-503039, by the Austrian-Hungarian Intergovernmental Cooperation (A14/04), by FP6-2003-LIFESCIHEALTH-I: Bio-Sim, by NKFP-MediChem2 1/A/005/2004, and by OTKA T-046071 to JO.GGK receives Bolyai fellowship.
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