Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71
Novel insights on proteins involved in Alzheimer’s disease (AD) are needed. Since multiple cell types and matrix components are altered in AD, bulk analysis of brain tissue maybe difficult to interpret. In the current study, we isolated pyramidal cells from the cornu ammonis 1 (CA1) region of the hi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-11-01
|
| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.735334/full |
| _version_ | 1798032030332616704 |
|---|---|
| author | Anna Sandebring-Matton Anna Sandebring-Matton Anna Sandebring-Matton Michael Axenhus Michael Axenhus Nenad Bogdanovic Nenad Bogdanovic Bengt Winblad Sophia Schedin-Weiss Per Nilsson Lars O. Tjernberg Lars O. Tjernberg |
| author_facet | Anna Sandebring-Matton Anna Sandebring-Matton Anna Sandebring-Matton Michael Axenhus Michael Axenhus Nenad Bogdanovic Nenad Bogdanovic Bengt Winblad Sophia Schedin-Weiss Per Nilsson Lars O. Tjernberg Lars O. Tjernberg |
| author_sort | Anna Sandebring-Matton |
| collection | DOAJ |
| description | Novel insights on proteins involved in Alzheimer’s disease (AD) are needed. Since multiple cell types and matrix components are altered in AD, bulk analysis of brain tissue maybe difficult to interpret. In the current study, we isolated pyramidal cells from the cornu ammonis 1 (CA1) region of the hippocampus from five AD and five neurologically healthy donors using laser capture microdissection (LCM). The samples were analyzed by proteomics using 18O-labeled internal standard and nano-high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for relative quantification. Fold change between AD and control was calculated for the proteins that were identified in at least two individual proteomes from each group. From the 10 cases analyzed, 62 proteins were identified in at least two AD cases and two control cases. Creatine kinase B-type (CKB), 14-3-3-γ, and heat shock cognate 71 (Hsc71), which have not been extensively studied in the context of the human AD brain previously, were selected for further studies by immunohistochemistry (IHC). In hippocampus, semi-quantitative measures of IHC staining of the three proteins confirmed the findings from our proteomic analysis. Studies of the same proteins in the frontal cortex revealed that the alterations remained for CKB and 14-3-3-γ but not for Hsc71. Protein upregulation in CA1 neurons of final stage AD is either a result of detrimental, pathological effects, or from cell-specific protective response mechanisms in surviving neurons. Based on previous findings from experimental studies, CKB and Hsc71 likely exhibit protective effects, whereas 14-3-3-γ may represent a detrimental pathway. These new players could reflect pathways of importance for the development of new therapeutic strategies. |
| first_indexed | 2024-04-11T20:06:09Z |
| format | Article |
| id | doaj.art-b8e169d732ac4e29afd84eac3f2589c9 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-11T20:06:09Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-b8e169d732ac4e29afd84eac3f2589c92022-12-22T04:05:18ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-11-011310.3389/fnagi.2021.735334735334Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71Anna Sandebring-Matton0Anna Sandebring-Matton1Anna Sandebring-Matton2Michael Axenhus3Michael Axenhus4Nenad Bogdanovic5Nenad Bogdanovic6Bengt Winblad7Sophia Schedin-Weiss8Per Nilsson9Lars O. Tjernberg10Lars O. Tjernberg11Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenAgeing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, United KingdomDivision of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenTheme Inflammation and Aging, Karolinska University Hospital, Huddinge, SwedenDivision of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenTheme Inflammation and Aging, Karolinska University Hospital, Huddinge, SwedenDivision of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenDivision of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenDivision of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenDivision of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenClinical Chemistry, Karolinska University Hospital, Solna, SwedenNovel insights on proteins involved in Alzheimer’s disease (AD) are needed. Since multiple cell types and matrix components are altered in AD, bulk analysis of brain tissue maybe difficult to interpret. In the current study, we isolated pyramidal cells from the cornu ammonis 1 (CA1) region of the hippocampus from five AD and five neurologically healthy donors using laser capture microdissection (LCM). The samples were analyzed by proteomics using 18O-labeled internal standard and nano-high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for relative quantification. Fold change between AD and control was calculated for the proteins that were identified in at least two individual proteomes from each group. From the 10 cases analyzed, 62 proteins were identified in at least two AD cases and two control cases. Creatine kinase B-type (CKB), 14-3-3-γ, and heat shock cognate 71 (Hsc71), which have not been extensively studied in the context of the human AD brain previously, were selected for further studies by immunohistochemistry (IHC). In hippocampus, semi-quantitative measures of IHC staining of the three proteins confirmed the findings from our proteomic analysis. Studies of the same proteins in the frontal cortex revealed that the alterations remained for CKB and 14-3-3-γ but not for Hsc71. Protein upregulation in CA1 neurons of final stage AD is either a result of detrimental, pathological effects, or from cell-specific protective response mechanisms in surviving neurons. Based on previous findings from experimental studies, CKB and Hsc71 likely exhibit protective effects, whereas 14-3-3-γ may represent a detrimental pathway. These new players could reflect pathways of importance for the development of new therapeutic strategies.https://www.frontiersin.org/articles/10.3389/fnagi.2021.735334/fullAlzheimer’s disease14-3-3-γcreatine kinase Bheat shock cognate 71laser capture microscopyproteomics |
| spellingShingle | Anna Sandebring-Matton Anna Sandebring-Matton Anna Sandebring-Matton Michael Axenhus Michael Axenhus Nenad Bogdanovic Nenad Bogdanovic Bengt Winblad Sophia Schedin-Weiss Per Nilsson Lars O. Tjernberg Lars O. Tjernberg Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71 Frontiers in Aging Neuroscience Alzheimer’s disease 14-3-3-γ creatine kinase B heat shock cognate 71 laser capture microscopy proteomics |
| title | Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71 |
| title_full | Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71 |
| title_fullStr | Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71 |
| title_full_unstemmed | Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71 |
| title_short | Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat Shock Cognate 71 |
| title_sort | microdissected pyramidal cell proteomics of alzheimer brain reveals alterations in creatine kinase b type 14 3 3 γ and heat shock cognate 71 |
| topic | Alzheimer’s disease 14-3-3-γ creatine kinase B heat shock cognate 71 laser capture microscopy proteomics |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.735334/full |
| work_keys_str_mv | AT annasandebringmatton microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT annasandebringmatton microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT annasandebringmatton microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT michaelaxenhus microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT michaelaxenhus microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT nenadbogdanovic microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT nenadbogdanovic microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT bengtwinblad microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT sophiaschedinweiss microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT pernilsson microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT larsotjernberg microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 AT larsotjernberg microdissectedpyramidalcellproteomicsofalzheimerbrainrevealsalterationsincreatinekinasebtype1433gandheatshockcognate71 |