Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration

Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D l...
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Autor*in:	Sonia Bellini [verfasserIn] Claudia Saraceno [verfasserIn] Luisa Benussi [verfasserIn] Andrea Geviti [verfasserIn] Antonio Longobardi [verfasserIn] Roland Nicsanu [verfasserIn] Sara Cimini [verfasserIn] Martina Ricci [verfasserIn] Laura Canafoglia [verfasserIn] Cinzia Coppola [verfasserIn] Gianfranco Puoti [verfasserIn] Giuliano Binetti [verfasserIn] Giacomina Rossi [verfasserIn] Roberta Ghidoni [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 23(2022), 18, p 10693
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:18, p 10693

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms231810693

Katalog-ID:	DOAJ033938601

Internformat


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520			\|a Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD.
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allfields	10.3390/ijms231810693 doi (DE-627)DOAJ033938601 (DE-599)DOAJad546297590c41e48546528c09493221 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Sonia Bellini verfasserin aut Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD. cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles Biology (General) Chemistry Claudia Saraceno verfasserin aut Luisa Benussi verfasserin aut Andrea Geviti verfasserin aut Antonio Longobardi verfasserin aut Roland Nicsanu verfasserin aut Sara Cimini verfasserin aut Martina Ricci verfasserin aut Laura Canafoglia verfasserin aut Cinzia Coppola verfasserin aut Gianfranco Puoti verfasserin aut Giuliano Binetti verfasserin aut Giacomina Rossi verfasserin aut Roberta Ghidoni verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10693 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10693 https://doi.org/10.3390/ijms231810693 kostenfrei https://doaj.org/article/ad546297590c41e48546528c09493221 kostenfrei https://www.mdpi.com/1422-0067/23/18/10693 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10693
spelling	10.3390/ijms231810693 doi (DE-627)DOAJ033938601 (DE-599)DOAJad546297590c41e48546528c09493221 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Sonia Bellini verfasserin aut Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD. cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles Biology (General) Chemistry Claudia Saraceno verfasserin aut Luisa Benussi verfasserin aut Andrea Geviti verfasserin aut Antonio Longobardi verfasserin aut Roland Nicsanu verfasserin aut Sara Cimini verfasserin aut Martina Ricci verfasserin aut Laura Canafoglia verfasserin aut Cinzia Coppola verfasserin aut Gianfranco Puoti verfasserin aut Giuliano Binetti verfasserin aut Giacomina Rossi verfasserin aut Roberta Ghidoni verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10693 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10693 https://doi.org/10.3390/ijms231810693 kostenfrei https://doaj.org/article/ad546297590c41e48546528c09493221 kostenfrei https://www.mdpi.com/1422-0067/23/18/10693 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10693
allfields_unstemmed	10.3390/ijms231810693 doi (DE-627)DOAJ033938601 (DE-599)DOAJad546297590c41e48546528c09493221 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Sonia Bellini verfasserin aut Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD. cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles Biology (General) Chemistry Claudia Saraceno verfasserin aut Luisa Benussi verfasserin aut Andrea Geviti verfasserin aut Antonio Longobardi verfasserin aut Roland Nicsanu verfasserin aut Sara Cimini verfasserin aut Martina Ricci verfasserin aut Laura Canafoglia verfasserin aut Cinzia Coppola verfasserin aut Gianfranco Puoti verfasserin aut Giuliano Binetti verfasserin aut Giacomina Rossi verfasserin aut Roberta Ghidoni verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10693 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10693 https://doi.org/10.3390/ijms231810693 kostenfrei https://doaj.org/article/ad546297590c41e48546528c09493221 kostenfrei https://www.mdpi.com/1422-0067/23/18/10693 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10693
allfieldsGer	10.3390/ijms231810693 doi (DE-627)DOAJ033938601 (DE-599)DOAJad546297590c41e48546528c09493221 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Sonia Bellini verfasserin aut Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD. cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles Biology (General) Chemistry Claudia Saraceno verfasserin aut Luisa Benussi verfasserin aut Andrea Geviti verfasserin aut Antonio Longobardi verfasserin aut Roland Nicsanu verfasserin aut Sara Cimini verfasserin aut Martina Ricci verfasserin aut Laura Canafoglia verfasserin aut Cinzia Coppola verfasserin aut Gianfranco Puoti verfasserin aut Giuliano Binetti verfasserin aut Giacomina Rossi verfasserin aut Roberta Ghidoni verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10693 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10693 https://doi.org/10.3390/ijms231810693 kostenfrei https://doaj.org/article/ad546297590c41e48546528c09493221 kostenfrei https://www.mdpi.com/1422-0067/23/18/10693 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10693
allfieldsSound	10.3390/ijms231810693 doi (DE-627)DOAJ033938601 (DE-599)DOAJad546297590c41e48546528c09493221 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Sonia Bellini verfasserin aut Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD. cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles Biology (General) Chemistry Claudia Saraceno verfasserin aut Luisa Benussi verfasserin aut Andrea Geviti verfasserin aut Antonio Longobardi verfasserin aut Roland Nicsanu verfasserin aut Sara Cimini verfasserin aut Martina Ricci verfasserin aut Laura Canafoglia verfasserin aut Cinzia Coppola verfasserin aut Gianfranco Puoti verfasserin aut Giuliano Binetti verfasserin aut Giacomina Rossi verfasserin aut Roberta Ghidoni verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 23(2022), 18, p 10693 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:23 year:2022 number:18, p 10693 https://doi.org/10.3390/ijms231810693 kostenfrei https://doaj.org/article/ad546297590c41e48546528c09493221 kostenfrei https://www.mdpi.com/1422-0067/23/18/10693 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 23 2022 18, p 10693
language	English
source	In International Journal of Molecular Sciences 23(2022), 18, p 10693 volume:23 year:2022 number:18, p 10693
sourceStr	In International Journal of Molecular Sciences 23(2022), 18, p 10693 volume:23 year:2022 number:18, p 10693
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Sonia Bellini @@aut@@ Claudia Saraceno @@aut@@ Luisa Benussi @@aut@@ Andrea Geviti @@aut@@ Antonio Longobardi @@aut@@ Roland Nicsanu @@aut@@ Sara Cimini @@aut@@ Martina Ricci @@aut@@ Laura Canafoglia @@aut@@ Cinzia Coppola @@aut@@ Gianfranco Puoti @@aut@@ Giuliano Binetti @@aut@@ Giacomina Rossi @@aut@@ Roberta Ghidoni @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ033938601
language_de	englisch
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callnumber-first	Q - Science
author	Sonia Bellini
spellingShingle	Sonia Bellini misc QH301-705.5 misc QD1-999 misc cathepsin D misc frontotemporal lobar degeneration misc endo-lysosomal pathway misc GRN misc C9orf72 misc extracellular vesicles misc Biology (General) misc Chemistry Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration
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topic_title	QH301-705.5 QD1-999 Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration cathepsin D frontotemporal lobar degeneration endo-lysosomal pathway GRN C9orf72 extracellular vesicles
topic	misc QH301-705.5 misc QD1-999 misc cathepsin D misc frontotemporal lobar degeneration misc endo-lysosomal pathway misc GRN misc C9orf72 misc extracellular vesicles misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc cathepsin D misc frontotemporal lobar degeneration misc endo-lysosomal pathway misc GRN misc C9orf72 misc extracellular vesicles misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc cathepsin D misc frontotemporal lobar degeneration misc endo-lysosomal pathway misc GRN misc C9orf72 misc extracellular vesicles misc Biology (General) misc Chemistry
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title	Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration
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title_full	Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration
author_sort	Sonia Bellini
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author_browse	Sonia Bellini Claudia Saraceno Luisa Benussi Andrea Geviti Antonio Longobardi Roland Nicsanu Sara Cimini Martina Ricci Laura Canafoglia Cinzia Coppola Gianfranco Puoti Giuliano Binetti Giacomina Rossi Roberta Ghidoni
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author-letter	Sonia Bellini
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author2-role	verfasserin
title_sort	plasma small extracellular vesicle cathepsin d dysregulation in <i<grn/c9orf72</i< and sporadic frontotemporal lobar degeneration
callnumber	QH301-705.5
title_auth	Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration
abstract	Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD.
abstractGer	Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD.
abstract_unstemmed	Emerging data suggest the roles of endo-lysosomal dysfunctions in frontotemporal lobar degeneration (FTLD) and in other dementias. Cathepsin D is one of the major lysosomal proteases, mediating the degradation of unfolded protein aggregates. In this retrospective study, we investigated cathepsin D levels in human plasma and in the plasma small extracellular vesicles (sEVs) of 161 subjects (40 sporadic FTLD, 33 intermediate/pathological <i<C9orf72</i< expansion carriers, 45 heterozygous/homozygous <i<GRN</i< mutation carriers, and 43 controls). Cathepsin D was quantified by ELISA, and nanoparticle tracking analysis data (sEV concentration for the cathepsin D level normalization) were extracted from our previously published dataset or were newly generated. First, we revealed a positive correlation of the cathepsin D levels with the age of the patients and controls. Even if no significant differences were found in the cathepsin D plasma levels, we observed a progressive reduction in plasma cathepsin D moving from the intermediate to <i<C9orf72</i< pathological expansion carriers. Observing the sEVs nano-compartment, we observed increased cathepsin D sEV cargo (ng/sEV) levels in genetic/sporadic FTLD. The diagnostic performance of this biomarker was fairly high (AUC = 0.85). Moreover, sEV and plasma cathepsin D levels were positively correlated with age at onset. In conclusion, our study further emphasizes the common occurrence of endo-lysosomal dysregulation in <i<GRN/C9orf72</i< and sporadic FTLD.
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title_short	Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration
url	https://doi.org/10.3390/ijms231810693 https://doaj.org/article/ad546297590c41e48546528c09493221 https://www.mdpi.com/1422-0067/23/18/10693 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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Plasma Small Extracellular Vesicle Cathepsin D Dysregulation in <i<GRN/C9orf72</i< and Sporadic Frontotemporal Lobar Degeneration

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