Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis
It is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer’s disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an add...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/11/5/583 |
| _version_ | 1797535663614066688 |
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| author | Jay S. Hanas James R. S. Hocker Christian A. Vannarath Megan R. Lerner Scott G. Blair Stan A. Lightfoot Rushie J. Hanas James R. Couch Linda A. Hershey |
| author_facet | Jay S. Hanas James R. S. Hocker Christian A. Vannarath Megan R. Lerner Scott G. Blair Stan A. Lightfoot Rushie J. Hanas James R. Couch Linda A. Hershey |
| author_sort | Jay S. Hanas |
| collection | DOAJ |
| description | It is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer’s disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an added benefit of such platforms. This study utilizes a simplified and novel serum profiling platform, using mass spectrometry (MS), to help distinguish AD patient groups (mild and moderate) and controls, as well as to aid in understanding of biochemical phenotypes and possible disease development. A comparison of discriminating sera mass peaks between AD patients and control individuals was performed using leave one [serum sample] out cross validation (LOOCV) combined with a novel peak classification valuation (PCV) procedure. LOOCV/PCV was able to distinguish significant sera mass peak differences between a group of mild AD patients and control individuals with a <i>p</i> value of 10<sup>−13</sup>. This value became non-significant (<i>p</i> = 0.09) when the same sera samples were randomly allocated between the two groups and reanalyzed by LOOCV/PCV. This is indicative of physiological group differences in the original true-pathology binary group comparison. Similarities and differences between AD patients and traumatic brain injury (TBI) patients were also discernable using this novel LOOCV/PCV platform. MS/MS peptide analysis was performed on serum mass peaks comparing mild AD patients with control individuals. Bioinformatics analysis suggested that cell pathways/biochemical phenotypes affected in AD include those involving neuronal cell death, vasculature, neurogenesis, and AD/dementia/amyloidosis. Inflammation, autoimmunity, autophagy, and blood–brain barrier pathways also appear to be relevant to AD. An impaired VWF/ADAMTS13 vasculature axis with connections to F8 (factor VIII) and LRP1 and NOTCH1 was indicated and is proposed to be important in AD development. |
| first_indexed | 2024-03-10T11:48:33Z |
| format | Article |
| id | doaj.art-cf15017443b5450a9d5cfb7b2f70ca97 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T11:48:33Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-cf15017443b5450a9d5cfb7b2f70ca972023-11-21T17:55:33ZengMDPI AGBrain Sciences2076-34252021-04-0111558310.3390/brainsci11050583Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 AxisJay S. Hanas0James R. S. Hocker1Christian A. Vannarath2Megan R. Lerner3Scott G. Blair4Stan A. Lightfoot5Rushie J. Hanas6James R. Couch7Linda A. Hershey8Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAVeterans Administration Hospital, Oklahoma City, OK 73104, USADepartment of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAIt is important to develop minimally invasive biomarker platforms to help in the identification and monitoring of patients with Alzheimer’s disease (AD). Assisting in the understanding of biochemical mechanisms as well as identifying potential novel biomarkers and therapeutic targets would be an added benefit of such platforms. This study utilizes a simplified and novel serum profiling platform, using mass spectrometry (MS), to help distinguish AD patient groups (mild and moderate) and controls, as well as to aid in understanding of biochemical phenotypes and possible disease development. A comparison of discriminating sera mass peaks between AD patients and control individuals was performed using leave one [serum sample] out cross validation (LOOCV) combined with a novel peak classification valuation (PCV) procedure. LOOCV/PCV was able to distinguish significant sera mass peak differences between a group of mild AD patients and control individuals with a <i>p</i> value of 10<sup>−13</sup>. This value became non-significant (<i>p</i> = 0.09) when the same sera samples were randomly allocated between the two groups and reanalyzed by LOOCV/PCV. This is indicative of physiological group differences in the original true-pathology binary group comparison. Similarities and differences between AD patients and traumatic brain injury (TBI) patients were also discernable using this novel LOOCV/PCV platform. MS/MS peptide analysis was performed on serum mass peaks comparing mild AD patients with control individuals. Bioinformatics analysis suggested that cell pathways/biochemical phenotypes affected in AD include those involving neuronal cell death, vasculature, neurogenesis, and AD/dementia/amyloidosis. Inflammation, autoimmunity, autophagy, and blood–brain barrier pathways also appear to be relevant to AD. An impaired VWF/ADAMTS13 vasculature axis with connections to F8 (factor VIII) and LRP1 and NOTCH1 was indicated and is proposed to be important in AD development.https://www.mdpi.com/2076-3425/11/5/583Alzheimer’s disease (AD)biochemical phenotype analysisserum profilingmass spectrometryVWF/ADAMTS13 axistraumatic brain injury (TBI) |
| spellingShingle | Jay S. Hanas James R. S. Hocker Christian A. Vannarath Megan R. Lerner Scott G. Blair Stan A. Lightfoot Rushie J. Hanas James R. Couch Linda A. Hershey Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis Brain Sciences Alzheimer’s disease (AD) biochemical phenotype analysis serum profiling mass spectrometry VWF/ADAMTS13 axis traumatic brain injury (TBI) |
| title | Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis |
| title_full | Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis |
| title_fullStr | Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis |
| title_full_unstemmed | Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis |
| title_short | Distinguishing Alzheimer’s Disease Patients and Biochemical Phenotype Analysis Using a Novel Serum Profiling Platform: Potential Involvement of the VWF/ADAMTS13 Axis |
| title_sort | distinguishing alzheimer s disease patients and biochemical phenotype analysis using a novel serum profiling platform potential involvement of the vwf adamts13 axis |
| topic | Alzheimer’s disease (AD) biochemical phenotype analysis serum profiling mass spectrometry VWF/ADAMTS13 axis traumatic brain injury (TBI) |
| url | https://www.mdpi.com/2076-3425/11/5/583 |
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