A molecular signature in blood identifies early Parkinson’s disease

<p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p< Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Molochnikov Leonid [verfasserIn] Rabey Jose M [verfasserIn] Dobronevsky Evgenya [verfasserIn] Bonucelli Ubaldo [verfasserIn] Ceravolo Roberto [verfasserIn] Frosini Daniela [verfasserIn] Grünblatt Edna [verfasserIn] Riederer Peter [verfasserIn] Jacob Christian [verfasserIn] Aharon-Peretz Judith [verfasserIn] Bashenko Yulia [verfasserIn] Youdim Moussa BH [verfasserIn] Mandel Silvia A [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2012

Schlagwörter:	Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis

Übergeordnetes Werk:	In: Molecular Neurodegeneration - BMC, 2007, 7(2012), 1, p 26
Übergeordnetes Werk:	volume:7 ; year:2012 ; number:1, p 26

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/1750-1326-7-26

Katalog-ID:	DOAJ050939890

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520			\|a <p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p<
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allfields	10.1186/1750-1326-7-26 doi (DE-627)DOAJ050939890 (DE-599)DOAJ685bba475e4549b8a6745e789d66aaeb DE-627 ger DE-627 rakwb eng RC346-429 RC952-954.6 Molochnikov Leonid verfasserin aut A molecular signature in blood identifies early Parkinson’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p< Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis Neurology. Diseases of the nervous system Geriatrics Rabey Jose M verfasserin aut Dobronevsky Evgenya verfasserin aut Bonucelli Ubaldo verfasserin aut Ceravolo Roberto verfasserin aut Frosini Daniela verfasserin aut Grünblatt Edna verfasserin aut Riederer Peter verfasserin aut Jacob Christian verfasserin aut Aharon-Peretz Judith verfasserin aut Bashenko Yulia verfasserin aut Youdim Moussa BH verfasserin aut Mandel Silvia A verfasserin aut In Molecular Neurodegeneration BMC, 2007 7(2012), 1, p 26 (DE-627)515978361 (DE-600)2244557-2 17501326 nnns volume:7 year:2012 number:1, p 26 https://doi.org/10.1186/1750-1326-7-26 kostenfrei https://doaj.org/article/685bba475e4549b8a6745e789d66aaeb kostenfrei http://www.jnrbm.com/content/7/1/26 kostenfrei https://doaj.org/toc/1750-1326 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 7 2012 1, p 26
spelling	10.1186/1750-1326-7-26 doi (DE-627)DOAJ050939890 (DE-599)DOAJ685bba475e4549b8a6745e789d66aaeb DE-627 ger DE-627 rakwb eng RC346-429 RC952-954.6 Molochnikov Leonid verfasserin aut A molecular signature in blood identifies early Parkinson’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p< Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis Neurology. Diseases of the nervous system Geriatrics Rabey Jose M verfasserin aut Dobronevsky Evgenya verfasserin aut Bonucelli Ubaldo verfasserin aut Ceravolo Roberto verfasserin aut Frosini Daniela verfasserin aut Grünblatt Edna verfasserin aut Riederer Peter verfasserin aut Jacob Christian verfasserin aut Aharon-Peretz Judith verfasserin aut Bashenko Yulia verfasserin aut Youdim Moussa BH verfasserin aut Mandel Silvia A verfasserin aut In Molecular Neurodegeneration BMC, 2007 7(2012), 1, p 26 (DE-627)515978361 (DE-600)2244557-2 17501326 nnns volume:7 year:2012 number:1, p 26 https://doi.org/10.1186/1750-1326-7-26 kostenfrei https://doaj.org/article/685bba475e4549b8a6745e789d66aaeb kostenfrei http://www.jnrbm.com/content/7/1/26 kostenfrei https://doaj.org/toc/1750-1326 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 7 2012 1, p 26
allfields_unstemmed	10.1186/1750-1326-7-26 doi (DE-627)DOAJ050939890 (DE-599)DOAJ685bba475e4549b8a6745e789d66aaeb DE-627 ger DE-627 rakwb eng RC346-429 RC952-954.6 Molochnikov Leonid verfasserin aut A molecular signature in blood identifies early Parkinson’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p< Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis Neurology. Diseases of the nervous system Geriatrics Rabey Jose M verfasserin aut Dobronevsky Evgenya verfasserin aut Bonucelli Ubaldo verfasserin aut Ceravolo Roberto verfasserin aut Frosini Daniela verfasserin aut Grünblatt Edna verfasserin aut Riederer Peter verfasserin aut Jacob Christian verfasserin aut Aharon-Peretz Judith verfasserin aut Bashenko Yulia verfasserin aut Youdim Moussa BH verfasserin aut Mandel Silvia A verfasserin aut In Molecular Neurodegeneration BMC, 2007 7(2012), 1, p 26 (DE-627)515978361 (DE-600)2244557-2 17501326 nnns volume:7 year:2012 number:1, p 26 https://doi.org/10.1186/1750-1326-7-26 kostenfrei https://doaj.org/article/685bba475e4549b8a6745e789d66aaeb kostenfrei http://www.jnrbm.com/content/7/1/26 kostenfrei https://doaj.org/toc/1750-1326 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 7 2012 1, p 26
allfieldsGer	10.1186/1750-1326-7-26 doi (DE-627)DOAJ050939890 (DE-599)DOAJ685bba475e4549b8a6745e789d66aaeb DE-627 ger DE-627 rakwb eng RC346-429 RC952-954.6 Molochnikov Leonid verfasserin aut A molecular signature in blood identifies early Parkinson’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p< Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis Neurology. Diseases of the nervous system Geriatrics Rabey Jose M verfasserin aut Dobronevsky Evgenya verfasserin aut Bonucelli Ubaldo verfasserin aut Ceravolo Roberto verfasserin aut Frosini Daniela verfasserin aut Grünblatt Edna verfasserin aut Riederer Peter verfasserin aut Jacob Christian verfasserin aut Aharon-Peretz Judith verfasserin aut Bashenko Yulia verfasserin aut Youdim Moussa BH verfasserin aut Mandel Silvia A verfasserin aut In Molecular Neurodegeneration BMC, 2007 7(2012), 1, p 26 (DE-627)515978361 (DE-600)2244557-2 17501326 nnns volume:7 year:2012 number:1, p 26 https://doi.org/10.1186/1750-1326-7-26 kostenfrei https://doaj.org/article/685bba475e4549b8a6745e789d66aaeb kostenfrei http://www.jnrbm.com/content/7/1/26 kostenfrei https://doaj.org/toc/1750-1326 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 7 2012 1, p 26
allfieldsSound	10.1186/1750-1326-7-26 doi (DE-627)DOAJ050939890 (DE-599)DOAJ685bba475e4549b8a6745e789d66aaeb DE-627 ger DE-627 rakwb eng RC346-429 RC952-954.6 Molochnikov Leonid verfasserin aut A molecular signature in blood identifies early Parkinson’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p< Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis Neurology. Diseases of the nervous system Geriatrics Rabey Jose M verfasserin aut Dobronevsky Evgenya verfasserin aut Bonucelli Ubaldo verfasserin aut Ceravolo Roberto verfasserin aut Frosini Daniela verfasserin aut Grünblatt Edna verfasserin aut Riederer Peter verfasserin aut Jacob Christian verfasserin aut Aharon-Peretz Judith verfasserin aut Bashenko Yulia verfasserin aut Youdim Moussa BH verfasserin aut Mandel Silvia A verfasserin aut In Molecular Neurodegeneration BMC, 2007 7(2012), 1, p 26 (DE-627)515978361 (DE-600)2244557-2 17501326 nnns volume:7 year:2012 number:1, p 26 https://doi.org/10.1186/1750-1326-7-26 kostenfrei https://doaj.org/article/685bba475e4549b8a6745e789d66aaeb kostenfrei http://www.jnrbm.com/content/7/1/26 kostenfrei https://doaj.org/toc/1750-1326 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 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 7 2012 1, p 26
language	English
source	In Molecular Neurodegeneration 7(2012), 1, p 26 volume:7 year:2012 number:1, p 26
sourceStr	In Molecular Neurodegeneration 7(2012), 1, p 26 volume:7 year:2012 number:1, p 26
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis Neurology. Diseases of the nervous system Geriatrics
isfreeaccess_bool	true
container_title	Molecular Neurodegeneration
authorswithroles_txt_mv	Molochnikov Leonid @@aut@@ Rabey Jose M @@aut@@ Dobronevsky Evgenya @@aut@@ Bonucelli Ubaldo @@aut@@ Ceravolo Roberto @@aut@@ Frosini Daniela @@aut@@ Grünblatt Edna @@aut@@ Riederer Peter @@aut@@ Jacob Christian @@aut@@ Aharon-Peretz Judith @@aut@@ Bashenko Yulia @@aut@@ Youdim Moussa BH @@aut@@ Mandel Silvia A @@aut@@
publishDateDaySort_date	2012-01-01T00:00:00Z
hierarchy_top_id	515978361
id	DOAJ050939890
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ050939890</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230308155516.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2012 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/1750-1326-7-26</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ050939890</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ685bba475e4549b8a6745e789d66aaeb</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC346-429</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC952-954.6</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Molochnikov Leonid</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="2"><subfield code="a">A molecular signature in blood identifies early Parkinson’s disease</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2012</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a"><p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. 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callnumber-first	R - Medicine
author	Molochnikov Leonid
spellingShingle	Molochnikov Leonid misc RC346-429 misc RC952-954.6 misc Alzheimer’s disease misc Sporadic Parkinson’s disease misc Blood Biomarker misc CSF Biomarkers misc E3 ubiquitin ligase misc SCF misc SKP1 misc Heat shock protein Hsc-70 misc Early diagnosis misc Neurology. Diseases of the nervous system misc Geriatrics A molecular signature in blood identifies early Parkinson’s disease
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topic_title	RC346-429 RC952-954.6 A molecular signature in blood identifies early Parkinson’s disease Alzheimer’s disease Sporadic Parkinson’s disease Blood Biomarker CSF Biomarkers E3 ubiquitin ligase SCF SKP1 Heat shock protein Hsc-70 Early diagnosis
topic	misc RC346-429 misc RC952-954.6 misc Alzheimer’s disease misc Sporadic Parkinson’s disease misc Blood Biomarker misc CSF Biomarkers misc E3 ubiquitin ligase misc SCF misc SKP1 misc Heat shock protein Hsc-70 misc Early diagnosis misc Neurology. Diseases of the nervous system misc Geriatrics
topic_unstemmed	misc RC346-429 misc RC952-954.6 misc Alzheimer’s disease misc Sporadic Parkinson’s disease misc Blood Biomarker misc CSF Biomarkers misc E3 ubiquitin ligase misc SCF misc SKP1 misc Heat shock protein Hsc-70 misc Early diagnosis misc Neurology. Diseases of the nervous system misc Geriatrics
topic_browse	misc RC346-429 misc RC952-954.6 misc Alzheimer’s disease misc Sporadic Parkinson’s disease misc Blood Biomarker misc CSF Biomarkers misc E3 ubiquitin ligase misc SCF misc SKP1 misc Heat shock protein Hsc-70 misc Early diagnosis misc Neurology. Diseases of the nervous system misc Geriatrics
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title	A molecular signature in blood identifies early Parkinson’s disease
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title_full	A molecular signature in blood identifies early Parkinson’s disease
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author_browse	Molochnikov Leonid Rabey Jose M Dobronevsky Evgenya Bonucelli Ubaldo Ceravolo Roberto Frosini Daniela Grünblatt Edna Riederer Peter Jacob Christian Aharon-Peretz Judith Bashenko Yulia Youdim Moussa BH Mandel Silvia A
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title_sort	molecular signature in blood identifies early parkinson’s disease
callnumber	RC346-429
title_auth	A molecular signature in blood identifies early Parkinson’s disease
abstract	<p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p<
abstractGer	<p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p<
abstract_unstemmed	<p<Abstract</p< <p<Background</p< <p<The search for biomarkers in Parkinson’s disease (PD) is crucial to identify the disease early and monitor the effectiveness of neuroprotective therapies. We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p<
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title_short	A molecular signature in blood identifies early Parkinson’s disease
url	https://doi.org/10.1186/1750-1326-7-26 https://doaj.org/article/685bba475e4549b8a6745e789d66aaeb http://www.jnrbm.com/content/7/1/26 https://doaj.org/toc/1750-1326
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We aim to assess whether a gene signature could be detected in blood from early/mild PD patients that could support the diagnosis of early PD, focusing on genes found particularly altered in the substantia nigra of sporadic PD.</p< <p<Results</p< <p<The transcriptional expression of seven selected genes was examined in blood samples from 62 early stage PD patients and 64 healthy age-matched controls. Stepwise multivariate logistic regression analysis identified five genes as optimal predictors of PD: p19 S-phase kinase-associated protein 1A (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.60–0.90), huntingtin interacting protein-2 (OR 1.32; CI 1.08–1.61), aldehyde dehydrogenase family 1 subfamily A1 (OR 0.86; 95% CI 0.75–0.99), 19 S proteasomal protein PSMC4 (OR 0.73; 95% CI 0.60–0.89) and heat shock 70-kDa protein 8 (OR 1.39; 95% CI 1.14–1.70). At a 0.5 cut-off the gene panel yielded a sensitivity and specificity in detecting PD of 90.3 and 89.1 respectively and the area under the receiving operating curve (ROC AUC) was 0.96. </p< <p<The performance of the five-gene classifier on the <it<de novo</it< PD individuals alone composing the early PD cohort (n = 38), resulted in a similar ROC with an AUC of 0.95, indicating the stability of the model and also, that patient medication had no significant effect on the predictive probability (PP) of the classifier for PD risk. The predictive ability of the model was validated in an independent cohort of 30 patients at advanced stage of PD, classifying correctly all cases as PD (100% sensitivity). Notably, the nominal average value of the PP for PD (0.95 (SD = 0.09)) in this cohort was higher than that of the early PD group (0.83 (SD = 0.22))<it<,</it< suggesting a potential for the model to assess disease severity. Lastly, the gene panel fully discriminated between PD and Alzheimer’s disease (n = 29).</p< <p<Conclusions</p< <p<The findings provide evidence on the ability of a five-gene panel to diagnose early/mild PD, with a possible diagnostic value for detection of asymptomatic PD before overt expression of the disorder.</p<</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Alzheimer’s disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Sporadic Parkinson’s disease</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Blood Biomarker</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">CSF Biomarkers</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">E3 ubiquitin ligase</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SCF</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">SKP1</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Heat shock protein Hsc-70</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Early diagnosis</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neurology. 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A molecular signature in blood identifies early Parkinson’s disease

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