ID

45907

Descrição

Principal Investigator: Mohammad Faghihi, MD, PhD, University of Miami, Miami, FL, USA MeSH: Parkinson Disease https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000901 There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis and monitoring disease progression. In this study we evaluated cerebrospinal fluid (CSF) proteins, which are known to be critically involved in PD or identified in our preliminary profiling studies, aptamers, and RNAs as potential PD biomarkers. Access to subjects for this study was via the Pacific Northwest Udall Center (PANUC) and the Alzheimer's Disease Research Center (ADRC) at the University of Washington and Oregon Health and Sciences University (OHSU). Using CSF samples from 30 well-characterized patients with PD and 30 age-, sex-matched healthy controls, we prepared RNA seq libraries and performed deep sequencing of all RNA species, including small and long RNA, mRNAs, noncoding RNAs and differentially spliced transcripts. We then tried several methods for RNAseq data analysis to optimize our analysis pipeline. We identified a total of 3381 transcripts corresponding to 182 long intergenic RNAs (LincRNAs), 11 microRNAs (miRNAs), 2861 protein-coding transcripts, 200 pseudogenes and 127 antisense RNAs; some of them were differentially expressed between PD and control groups. Selected differentially expressed RNAs have been validated in the same set of CSF samples using real-time PCR (RT-PCR). Further validations in independent, larger cohorts of samples are still ongoing. Our results obtained so far suggested that CSF proteins and RNAs could be used as good indexes for PD diagnosis and disease severity/progression. This study is a part of the NIDDS-funded Parkinson's Disease Biomarkers Program (PDBP).

Link

dbGaP study = phs000901

Palavras-chave

Versões (1)
  1. 17/01/2024 17/01/2024 - Simon Heim
Titular dos direitos

Mohammad Faghihi, MD, PhD, University of Miami, Miami, FL, USA

Transferido a

17 de janeiro de 2024

DOI

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Licença

Creative Commons BY 4.0
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dbGaP phs000901 University of Washington CSF biomarker study for Parkinson disease

Inglês

Eligibility Criteria

5 Formulários  
Inclusion and exclusion criteria
Descrição

Inclusion and exclusion criteria

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0680251
*Parkinson Disease (PD)*: All patients meet UK PD Society Brain Bank clinical diagnostic criteria for PD (Gibb et al., 1988) except that having "more than one affected relative" is not considered an exclusion criterion. In order to exclude dementia disorders other than PD with dementia (PD-D), a multi-tiered strategy was used: First, subjects with dementia with Lewy Bodies (DLB) have been excluded based on the diagnostic definition; in order to be diagnosed with PD or PD-D, subjects must present with motor symptoms AT LEAST ONE YEAR prior to the onset of dementia. This criterion excludes those with DLB, in which dementia is present at diagnosis. To exclude subjects with Alzheimer disease (AD)-like pathology, we test the cerebrospinal fluid (CSF) samples collected for all subjects for Aß and tau proteins, levels of which are sensitive biomarkers for AD. Subjects whose levels do not meet the cutoffs determined by our lab and others (Montine et al., 2010; Li et al., 2007; Fagan et al., 2007) are excluded. To limit inclusion of subjects with vascular dementia, we have excluded from our cohort patients with history of known stroke or other vascular diseases. Additionally, we determine Hachinski scores of all subjects, and exclude subjects based on established cutoffs (Moroney et al., 1997); the score may also be included as a covariate in the analysis to limit influence of vascular symptoms.
Descrição

*Parkinson Disease (PD)*: All patients meet UK PD Society Brain Bank clinical diagnostic criteria for PD (Gibb et al., 1988) except that having "more than one affected relative" is not considered an exclusion criterion. In order to exclude dementia disorders other than PD with dementia (PD-D), a multi-tiered strategy was used: First, subjects with dementia with Lewy Bodies (DLB) have been excluded based on the diagnostic definition; in order to be diagnosed with PD or PD-D, subjects must present with motor symptoms AT LEAST ONE YEAR prior to the onset of dementia. This criterion excludes those with DLB, in which dementia is present at diagnosis. To exclude subjects with Alzheimer disease (AD)-like pathology, we test the cerebrospinal fluid (CSF) samples collected for all subjects for Aß and tau proteins, levels of which are sensitive biomarkers for AD. Subjects whose levels do not meet the cutoffs determined by our lab and others (Montine et al., 2010; Li et al., 2007; Fagan et al., 2007) are excluded. To limit inclusion of subjects with vascular dementia, we have excluded from our cohort patients with history of known stroke or other vascular diseases. Additionally, we determine Hachinski scores of all subjects, and exclude subjects based on established cutoffs (Moroney et al., 1997); the score may also be included as a covariate in the analysis to limit influence of vascular symptoms.

Tipo de dados

boolean

Alias
UMLS CUI [1,1]
C0030567
UMLS CUI [1,2]
C0871251
UMLS CUI [1,3]
C0332300
UMLS CUI [1,4]
C5142998
UMLS CUI [1,5]
C1518469
UMLS CUI [1,6]
C1518422
UMLS CUI [2,1]
C0680251
UMLS CUI [2,2]
C0497327
UMLS CUI [2,3]
C1828079
UMLS CUI [2,4]
C0679199
UMLS CUI [3,1]
C0752347
UMLS CUI [3,2]
C0680251
UMLS CUI [3,3]
C0011900
UMLS CUI [3,4]
C0426980
UMLS CUI [3,5]
C0332152
UMLS CUI [3,6]
C0332162
UMLS CUI [3,7]
C0497327
UMLS CUI [4,1]
C0680251
UMLS CUI [4,2]
C0002395
UMLS CUI [4,3]
C0007806
UMLS CUI [4,4]
C0039593
UMLS CUI [4,5]
C0085401
UMLS CUI [4,6]
C0078939
UMLS CUI [4,7]
C2349100
UMLS CUI [5,1]
C0680251
UMLS CUI [5,2]
C3828770
UMLS CUI [5,3]
C1442160
UMLS CUI [6,1]
C0680253
UMLS CUI [6,2]
C0449295
UMLS CUI [6,3]
C0011269
UMLS CUI [6,4]
C0680251
UMLS CUI [6,5]
C0262926
UMLS CUI [6,6]
C0038454
UMLS CUI [6,7]
C0042373
UMLS CUI [6,8]
C0475492
UMLS CUI [6,9]
C1442160
*Controls*: Control subjects are either spouses of patients in the PD or AD cohorts or community volunteers recruited from several sources (e.g., Veterans Service Organizations, the VA Voluntary Service Program, and local senior centers). This has allowed us to generate a control cohort that is well matched with our PD/AD cohorts in terms of demographic characteristics including age, sex, and education. All control volunteers undergo motor and cognitive evaluation by a trained clinician. They have no signs or symptoms suggesting cognitive impairment or neurological disease. Subjects with Montreal Cognitive Assessment (MoCA) scores less than 26 are excluded. Subjects with motor Unified Parkinson Disease Rating Scale (UPDRS) scores greater than 5 will be referred to a movement disorder specialist for detailed evaluation, and excluded if there are further concerns. Finally, it should be emphasized that although pathological confirmation has not been obtained in most subjects, all of them have been followed for 12 months or longer (median of 3 years) without demonstrating any symptoms or signs of neurological disorders, including mild cognitive impairment. It should also be noted that we have used these controls for many of our previous publications cited in the proposal, i.e., rich clinical data is available for this well-characterized cohort.
Descrição

*Controls*: Control subjects are either spouses of patients in the PD or AD cohorts or community volunteers recruited from several sources (e.g., Veterans Service Organizations, the VA Voluntary Service Program, and local senior centers). This has allowed us to generate a control cohort that is well matched with our PD/AD cohorts in terms of demographic characteristics including age, sex, and education. All control volunteers undergo motor and cognitive evaluation by a trained clinician. They have no signs or symptoms suggesting cognitive impairment or neurological disease. Subjects with Montreal Cognitive Assessment (MoCA) scores less than 26 are excluded. Subjects with motor Unified Parkinson Disease Rating Scale (UPDRS) scores greater than 5 will be referred to a movement disorder specialist for detailed evaluation, and excluded if there are further concerns. Finally, it should be emphasized that although pathological confirmation has not been obtained in most subjects, all of them have been followed for 12 months or longer (median of 3 years) without demonstrating any symptoms or signs of neurological disorders, including mild cognitive impairment. It should also be noted that we have used these controls for many of our previous publications cited in the proposal, i.e., rich clinical data is available for this well-characterized cohort.

Tipo de dados

boolean

Alias
UMLS CUI [1,1]
C0009932
UMLS CUI [1,2]
C0162409
UMLS CUI [1,3]
C0030705
UMLS CUI [1,4]
C0030567
UMLS CUI [1,5]
C0002395
UMLS CUI [1,6]
C1708335
UMLS CUI [1,7]
C0449416
UMLS CUI [1,8]
C1520061
UMLS CUI [2,1]
C1706214
UMLS CUI [2,2]
C0009932
UMLS CUI [2,3]
C0150103
UMLS CUI [2,4]
C0683970
UMLS CUI [2,5]
C0001779
UMLS CUI [2,6]
C1522384
UMLS CUI [2,7]
C0013658
UMLS CUI [3,1]
C1708335
UMLS CUI [3,2]
C1516691
UMLS CUI [3,3]
C0220825
UMLS CUI [3,4]
C0027853
UMLS CUI [3,5]
C0871685
UMLS CUI [4,1]
C1708335
UMLS CUI [4,2]
C3846032
UMLS CUI [4,3]
C0338656
UMLS CUI [4,4]
C0027765
UMLS CUI [5,1]
C3496286
UMLS CUI [5,2]
C0559741
UMLS CUI [5,3]
C0439092
UMLS CUI [5,4]
C1442160
UMLS CUI [5,5]
C2828389
UMLS CUI [6,1]
C3639721
UMLS CUI [6,2]
C0439093
UMLS CUI [6,3]
C1442160
UMLS CUI [6,4]
C0205543
UMLS CUI [6,5]
C0026650
UMLS CUI [6,6]
C0087009
UMLS CUI [6,7]
C0220825
UMLS CUI [6,8]
C2828389
UMLS CUI [7,1]
C5447879
UMLS CUI [7,2]
C1882120
UMLS CUI [7,3]
C0205393
UMLS CUI [7,4]
C0080105
UMLS CUI [7,5]
C4745109
UMLS CUI [7,6]
C0231221
UMLS CUI [7,7]
C0027765
UMLS CUI [7,8]
C1270972
UMLS CUI [8,1]
C0009932
UMLS CUI [8,2]
C0205156
UMLS CUI [8,3]
C0034036
UMLS CUI [8,4]
C0470187
UMLS CUI [8,5]
C1516606
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Similar models

Eligibility Criteria

5 Formulários
Name
Tipo
Description | Question | Decode (Coded Value)
Tipo de dados
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
*Parkinson Disease (PD)*: All patients meet UK PD Society Brain Bank clinical diagnostic criteria for PD (Gibb et al., 1988) except that having "more than one affected relative" is not considered an exclusion criterion. In order to exclude dementia disorders other than PD with dementia (PD-D), a multi-tiered strategy was used: First, subjects with dementia with Lewy Bodies (DLB) have been excluded based on the diagnostic definition; in order to be diagnosed with PD or PD-D, subjects must present with motor symptoms AT LEAST ONE YEAR prior to the onset of dementia. This criterion excludes those with DLB, in which dementia is present at diagnosis. To exclude subjects with Alzheimer disease (AD)-like pathology, we test the cerebrospinal fluid (CSF) samples collected for all subjects for Aß and tau proteins, levels of which are sensitive biomarkers for AD. Subjects whose levels do not meet the cutoffs determined by our lab and others (Montine et al., 2010; Li et al., 2007; Fagan et al., 2007) are excluded. To limit inclusion of subjects with vascular dementia, we have excluded from our cohort patients with history of known stroke or other vascular diseases. Additionally, we determine Hachinski scores of all subjects, and exclude subjects based on established cutoffs (Moroney et al., 1997); the score may also be included as a covariate in the analysis to limit influence of vascular symptoms.
Item
*Parkinson Disease (PD)*: All patients meet UK PD Society Brain Bank clinical diagnostic criteria for PD (Gibb et al., 1988) except that having "more than one affected relative" is not considered an exclusion criterion. In order to exclude dementia disorders other than PD with dementia (PD-D), a multi-tiered strategy was used: First, subjects with dementia with Lewy Bodies (DLB) have been excluded based on the diagnostic definition; in order to be diagnosed with PD or PD-D, subjects must present with motor symptoms AT LEAST ONE YEAR prior to the onset of dementia. This criterion excludes those with DLB, in which dementia is present at diagnosis. To exclude subjects with Alzheimer disease (AD)-like pathology, we test the cerebrospinal fluid (CSF) samples collected for all subjects for Aß and tau proteins, levels of which are sensitive biomarkers for AD. Subjects whose levels do not meet the cutoffs determined by our lab and others (Montine et al., 2010; Li et al., 2007; Fagan et al., 2007) are excluded. To limit inclusion of subjects with vascular dementia, we have excluded from our cohort patients with history of known stroke or other vascular diseases. Additionally, we determine Hachinski scores of all subjects, and exclude subjects based on established cutoffs (Moroney et al., 1997); the score may also be included as a covariate in the analysis to limit influence of vascular symptoms.
boolean
C0030567 (UMLS CUI [1,1])
C0871251 (UMLS CUI [1,2])
C0332300 (UMLS CUI [1,3])
C5142998 (UMLS CUI [1,4])
C1518469 (UMLS CUI [1,5])
C1518422 (UMLS CUI [1,6])
C0680251 (UMLS CUI [2,1])
C0497327 (UMLS CUI [2,2])
C1828079 (UMLS CUI [2,3])
C0679199 (UMLS CUI [2,4])
C0752347 (UMLS CUI [3,1])
C0680251 (UMLS CUI [3,2])
C0011900 (UMLS CUI [3,3])
C0426980 (UMLS CUI [3,4])
C0332152 (UMLS CUI [3,5])
C0332162 (UMLS CUI [3,6])
C0497327 (UMLS CUI [3,7])
C0680251 (UMLS CUI [4,1])
C0002395 (UMLS CUI [4,2])
C0007806 (UMLS CUI [4,3])
C0039593 (UMLS CUI [4,4])
C0085401 (UMLS CUI [4,5])
C0078939 (UMLS CUI [4,6])
C2349100 (UMLS CUI [4,7])
C0680251 (UMLS CUI [5,1])
C3828770 (UMLS CUI [5,2])
C1442160 (UMLS CUI [5,3])
C0680253 (UMLS CUI [6,1])
C0449295 (UMLS CUI [6,2])
C0011269 (UMLS CUI [6,3])
C0680251 (UMLS CUI [6,4])
C0262926 (UMLS CUI [6,5])
C0038454 (UMLS CUI [6,6])
C0042373 (UMLS CUI [6,7])
C0475492 (UMLS CUI [6,8])
C1442160 (UMLS CUI [6,9])
*Controls*: Control subjects are either spouses of patients in the PD or AD cohorts or community volunteers recruited from several sources (e.g., Veterans Service Organizations, the VA Voluntary Service Program, and local senior centers). This has allowed us to generate a control cohort that is well matched with our PD/AD cohorts in terms of demographic characteristics including age, sex, and education. All control volunteers undergo motor and cognitive evaluation by a trained clinician. They have no signs or symptoms suggesting cognitive impairment or neurological disease. Subjects with Montreal Cognitive Assessment (MoCA) scores less than 26 are excluded. Subjects with motor Unified Parkinson Disease Rating Scale (UPDRS) scores greater than 5 will be referred to a movement disorder specialist for detailed evaluation, and excluded if there are further concerns. Finally, it should be emphasized that although pathological confirmation has not been obtained in most subjects, all of them have been followed for 12 months or longer (median of 3 years) without demonstrating any symptoms or signs of neurological disorders, including mild cognitive impairment. It should also be noted that we have used these controls for many of our previous publications cited in the proposal, i.e., rich clinical data is available for this well-characterized cohort.
Item
*Controls*: Control subjects are either spouses of patients in the PD or AD cohorts or community volunteers recruited from several sources (e.g., Veterans Service Organizations, the VA Voluntary Service Program, and local senior centers). This has allowed us to generate a control cohort that is well matched with our PD/AD cohorts in terms of demographic characteristics including age, sex, and education. All control volunteers undergo motor and cognitive evaluation by a trained clinician. They have no signs or symptoms suggesting cognitive impairment or neurological disease. Subjects with Montreal Cognitive Assessment (MoCA) scores less than 26 are excluded. Subjects with motor Unified Parkinson Disease Rating Scale (UPDRS) scores greater than 5 will be referred to a movement disorder specialist for detailed evaluation, and excluded if there are further concerns. Finally, it should be emphasized that although pathological confirmation has not been obtained in most subjects, all of them have been followed for 12 months or longer (median of 3 years) without demonstrating any symptoms or signs of neurological disorders, including mild cognitive impairment. It should also be noted that we have used these controls for many of our previous publications cited in the proposal, i.e., rich clinical data is available for this well-characterized cohort.
boolean
C0009932 (UMLS CUI [1,1])
C0162409 (UMLS CUI [1,2])
C0030705 (UMLS CUI [1,3])
C0030567 (UMLS CUI [1,4])
C0002395 (UMLS CUI [1,5])
C1708335 (UMLS CUI [1,6])
C0449416 (UMLS CUI [1,7])
C1520061 (UMLS CUI [1,8])
C1706214 (UMLS CUI [2,1])
C0009932 (UMLS CUI [2,2])
C0150103 (UMLS CUI [2,3])
C0683970 (UMLS CUI [2,4])
C0001779 (UMLS CUI [2,5])
C1522384 (UMLS CUI [2,6])
C0013658 (UMLS CUI [2,7])
C1708335 (UMLS CUI [3,1])
C1516691 (UMLS CUI [3,2])
C0220825 (UMLS CUI [3,3])
C0027853 (UMLS CUI [3,4])
C0871685 (UMLS CUI [3,5])
C1708335 (UMLS CUI [4,1])
C3846032 (UMLS CUI [4,2])
C0338656 (UMLS CUI [4,3])
C0027765 (UMLS CUI [4,4])
C3496286 (UMLS CUI [5,1])
C0559741 (UMLS CUI [5,2])
C0439092 (UMLS CUI [5,3])
C1442160 (UMLS CUI [5,4])
C2828389 (UMLS CUI [5,5])
C3639721 (UMLS CUI [6,1])
C0439093 (UMLS CUI [6,2])
C1442160 (UMLS CUI [6,3])
C0205543 (UMLS CUI [6,4])
C0026650 (UMLS CUI [6,5])
C0087009 (UMLS CUI [6,6])
C0220825 (UMLS CUI [6,7])
C2828389 (UMLS CUI [6,8])
C5447879 (UMLS CUI [7,1])
C1882120 (UMLS CUI [7,2])
C0205393 (UMLS CUI [7,3])
C0080105 (UMLS CUI [7,4])
C4745109 (UMLS CUI [7,5])
C0231221 (UMLS CUI [7,6])
C0027765 (UMLS CUI [7,7])
C1270972 (UMLS CUI [7,8])
C0009932 (UMLS CUI [8,1])
C0205156 (UMLS CUI [8,2])
C0034036 (UMLS CUI [8,3])
C0470187 (UMLS CUI [8,4])
C1516606 (UMLS CUI [8,5])
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