Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved]
Background: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological c...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2018-07-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/7-1012/v1 |
| _version_ | 1811331548743467008 |
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| author | Ilijana Begcevic Magda Tsolaki Davor Brinc Marshall Brown Eduardo Martinez-Morillo Ioulietta Lazarou Mahi Kozori Fani Tagaraki Stella Nenopoulou Mara Gkioka Eutichia Lazarou Bryant Lim Ihor Batruch Eleftherios P. Diamandis |
| author_facet | Ilijana Begcevic Magda Tsolaki Davor Brinc Marshall Brown Eduardo Martinez-Morillo Ioulietta Lazarou Mahi Kozori Fani Tagaraki Stella Nenopoulou Mara Gkioka Eutichia Lazarou Bryant Lim Ihor Batruch Eleftherios P. Diamandis |
| author_sort | Ilijana Begcevic |
| collection | DOAJ |
| description | Background: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain; amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific proteins as potential biomarkers of progression of AD. Methods: Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) and mild, moderate and severe AD dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe dementia) was observed for protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR protein in CSF is a novel potential biomarker of AD progression and could have important utility in assessing treatment success in clinical trials. |
| first_indexed | 2024-04-13T16:22:18Z |
| format | Article |
| id | doaj.art-c303716352c94c599bcc12cbb434edf6 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-04-13T16:22:18Z |
| publishDate | 2018-07-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-c303716352c94c599bcc12cbb434edf62022-12-22T02:39:51ZengF1000 Research LtdF1000Research2046-14022018-07-01710.12688/f1000research.15095.116440Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved]Ilijana Begcevic0Magda Tsolaki1Davor Brinc2Marshall Brown3Eduardo Martinez-Morillo4Ioulietta Lazarou5Mahi Kozori6Fani Tagaraki7Stella Nenopoulou8Mara Gkioka9Eutichia Lazarou10Bryant Lim11Ihor Batruch12Eleftherios P. Diamandis13Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, GreeceDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA, USALaboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central, Oviedo, Spain1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece1st Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, GreeceDepartment of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaBackground: Alzheimer’s disease (AD) is the most common type of dementia, with progressive onset of clinical symptoms. The main pathological hallmarks are brain deposits of extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). Cerebrospinal fluid reflects pathological changes in the brain; amyloid beta 1-42 is a marker of amyloid plaques, while total and phosphorylated tau are markers of NFT formation. Additional biomarkers associated with disease pathogenesis are needed, for better prognosis, more specific diagnosis, prediction of disease severity and progression and for improved patient classification in clinical trials. The aim of the present study was to evaluate brain-specific proteins as potential biomarkers of progression of AD. Methods: Overall, 30 candidate proteins were quantified in cerebrospinal fluid (CSF) samples from patients with mild cognitive impairment (MCI) and mild, moderate and severe AD dementia (n=101) using mass spectrometry-based selected reaction monitoring assays. ELISA was used for neuronal pentraxin receptor-1 (NPTXR) confirmation. Results: The best discrimination between MCI and more advanced AD stages (moderate and severe dementia) was observed for protein NPTXR (area under the curve, AUC=0.799). A statistically different abundance of this protein was observed between the two groups, with severe AD patients having progressively lower levels (p<0.05). ELISA confirmed lower levels in AD, in a separate cohort that included controls, MCI and AD patients. Conclusions: We conclude that NPTXR protein in CSF is a novel potential biomarker of AD progression and could have important utility in assessing treatment success in clinical trials.https://f1000research.com/articles/7-1012/v1 |
| spellingShingle | Ilijana Begcevic Magda Tsolaki Davor Brinc Marshall Brown Eduardo Martinez-Morillo Ioulietta Lazarou Mahi Kozori Fani Tagaraki Stella Nenopoulou Mara Gkioka Eutichia Lazarou Bryant Lim Ihor Batruch Eleftherios P. Diamandis Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved] F1000Research |
| title | Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved] |
| title_full | Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved] |
| title_fullStr | Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved] |
| title_full_unstemmed | Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved] |
| title_short | Neuronal pentraxin receptor-1 is a new cerebrospinal fluid biomarker of Alzheimer’s disease progression [version 1; referees: 3 approved] |
| title_sort | neuronal pentraxin receptor 1 is a new cerebrospinal fluid biomarker of alzheimer s disease progression version 1 referees 3 approved |
| url | https://f1000research.com/articles/7-1012/v1 |
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