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4. Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.

Author

Schrader, Joseph M, Majchrzak, Mark, Xu, Feng, Lee, Hedok, Agostinucci, Kevin, Davis, Judianne, Benveniste, Helene, and Van Nostrand, William E

Subjects
*TRANSFORMING growth factors-beta, *LABORATORY rats, *CEREBRAL amyloid angiopathy, *ALZHEIMER'S disease, *MAGNETIC resonance imaging
Abstract

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid β-protein (Aβ) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aβ promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-β1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-β1 pathway and increased TGF-β1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-β1 in the disease process. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Elevated expression of urokinase plasminogen activator in rodent models and patients with cerebral amyloid angiopathy

Author

Vervuurt, Marc, primary, Zhu, Xiaoyue, additional, Schrader, Joseph, additional, Kort, Anna M., additional, Marques, Tainá M., additional, Kersten, Iris, additional, Peters van Ton, Annemieke M., additional, Abdo, Wilson F., additional, Schreuder, Floris H. B. M., additional, Rasing, Ingeborg, additional, Terwindt, Gisela M., additional, Wermer, Marieke J. H., additional, Greenberg, Steven M., additional, Klijn, Catharina J. M., additional, Kuiperij, H. Bea, additional, Van Nostrand, William E., additional, and Verbeek, Marcel M., additional

Published
2022
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11. Elevated Expression of Urokinase Plasminogen Activator in Rodent Models and Patients With Cerebral Amyloid Angiopathy

Author

Vervuurt, Marc, primary, Zhu, Xiaoyue, additional, Schrader, Joseph, additional, de Kort, Anna, additional, Marques, Tainá, additional, Kersten, Iris, additional, Ton, Annemieke Peters van, additional, Abdo, Wilson, additional, Schreuder, Floris, additional, Rasing, Ingeborg, additional, Terwindt, Gisela, additional, Wermer, Marieke, additional, Greenberg, Steven, additional, Klijn, Catharina, additional, Kuiperij, Bea, additional, Nostrand, William Van, additional, and Verbeek, Marcel, additional

Published
2021
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13. sj-pdf-3-jcb-10.1177_0271678X20944226 - Supplemental material for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy

Author

Hedok Lee, Xu, Feng, Xiaodan Liu, Koundal, Sunil, Xiaoyue Zhu, Judianne Davis, Yanez, David, Schrader, Joseph, Stanisavljevic, Aleksandra, Rothman, Douglas L, Wardlaw, Joanna, Nostrand, William E Van, and Benveniste, Helene

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-3-jcb-10.1177_0271678X20944226 for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy by Hedok Lee, Feng Xu, Xiaodan Liu, Sunil Koundal, Xiaoyue Zhu, Judianne Davis, David Yanez, Joseph Schrader, Aleksandra Stanisavljevic, Douglas L Rothman, Joanna Wardlaw, William E Van Nostrand and Helene Benveniste in Journal of Cerebral Blood Flow & Metabolism

Published
2020
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14. sj-pdf-1-jcb-10.1177_0271678X20944226 - Supplemental material for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy

Author

Hedok Lee, Xu, Feng, Xiaodan Liu, Koundal, Sunil, Xiaoyue Zhu, Judianne Davis, Yanez, David, Schrader, Joseph, Stanisavljevic, Aleksandra, Rothman, Douglas L, Wardlaw, Joanna, Nostrand, William E Van, and Benveniste, Helene

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X20944226 for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy by Hedok Lee, Feng Xu, Xiaodan Liu, Sunil Koundal, Xiaoyue Zhu, Judianne Davis, David Yanez, Joseph Schrader, Aleksandra Stanisavljevic, Douglas L Rothman, Joanna Wardlaw, William E Van Nostrand and Helene Benveniste in Journal of Cerebral Blood Flow & Metabolism

Published
2020
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15. sj-pdf-4-jcb-10.1177_0271678X20944226 - Supplemental material for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy

Author

Hedok Lee, Xu, Feng, Xiaodan Liu, Koundal, Sunil, Xiaoyue Zhu, Judianne Davis, Yanez, David, Schrader, Joseph, Stanisavljevic, Aleksandra, Rothman, Douglas L, Wardlaw, Joanna, Nostrand, William E Van, and Benveniste, Helene

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-4-jcb-10.1177_0271678X20944226 for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy by Hedok Lee, Feng Xu, Xiaodan Liu, Sunil Koundal, Xiaoyue Zhu, Judianne Davis, David Yanez, Joseph Schrader, Aleksandra Stanisavljevic, Douglas L Rothman, Joanna Wardlaw, William E Van Nostrand and Helene Benveniste in Journal of Cerebral Blood Flow & Metabolism

Published
2020
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16. sj-pdf-2-jcb-10.1177_0271678X20944226 - Supplemental material for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy

Author

Hedok Lee, Xu, Feng, Xiaodan Liu, Koundal, Sunil, Xiaoyue Zhu, Judianne Davis, Yanez, David, Schrader, Joseph, Stanisavljevic, Aleksandra, Rothman, Douglas L, Wardlaw, Joanna, Nostrand, William E Van, and Benveniste, Helene

Subjects
110320 Radiology and Organ Imaging, FOS: Clinical medicine, FOS: Biological sciences, Medicine, Cell Biology, 110305 Emergency Medicine, 110306 Endocrinology, Biochemistry, 69999 Biological Sciences not elsewhere classified, 110904 Neurology and Neuromuscular Diseases, Neuroscience
Abstract

Supplemental material, sj-pdf-2-jcb-10.1177_0271678X20944226 for Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy by Hedok Lee, Feng Xu, Xiaodan Liu, Sunil Koundal, Xiaoyue Zhu, Judianne Davis, David Yanez, Joseph Schrader, Aleksandra Stanisavljevic, Douglas L Rothman, Joanna Wardlaw, William E Van Nostrand and Helene Benveniste in Journal of Cerebral Blood Flow & Metabolism

Published
2020
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17. Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy

Author

Lee, Hedok, primary, Xu, Feng, additional, Liu, Xiaodan, additional, Koundal, Sunil, additional, Zhu, Xiaoyue, additional, Davis, Judianne, additional, Yanez, David, additional, Schrader, Joseph, additional, Stanisavljevic, Aleksandra, additional, Rothman, Douglas L, additional, Wardlaw, Joanna, additional, Van Nostrand, William E, additional, and Benveniste, Helene, additional

Published
2020
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18. The differential actions of clozapine and other antipsychotic drugs on the translocation of dopamine D2 receptors to the cell surface

Author

Schrader, Joseph M., primary, Irving, Craig M., additional, Octeau, J. Christopher, additional, Christian, Joseph A., additional, Aballo, Timothy J., additional, Kareemo, Dean J., additional, Conti, Joseph, additional, Camberg, Jodi L., additional, Lane, J. Robert, additional, Javitch, Jonathan A., additional, and Kovoor, Abraham, additional

Published
2019
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19. Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy.

Author

Lee, Hedok, Xu, Feng, Liu, Xiaodan, Koundal, Sunil, Zhu, Xiaoyue, Davis, Judianne, Yanez, David, Schrader, Joseph, Stanisavljevic, Aleksandra, Rothman, Douglas L, Wardlaw, Joanna, Van Nostrand, William E, and Benveniste, Helene

Abstract

Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aβ deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss. [ABSTRACT FROM AUTHOR]

Published
2021
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22. Security first: providing safe environment a primary goal

Author

Schrader, Joseph

Subjects
Shopping centers -- Safety and security measures, Business, Retail industry
Abstract

Leading developers discuss security, avoiding cookie-cutter centers, the off-price/traditional anchor marriage and customer convenience To serve and protect ... it's a phrase that describes the basic purpose of any police [...]

Published
1992

25. Emergent White Matter Degeneration in the rTg-DI Rat Model of Cerebral Amyloid Angiopathy Exhibits Unique Proteomic Changes

Author

Schrader, Joseph M., Xu, Feng, Lee, Hedok, Barlock, Benjamin, Benveniste, Helene, and Van Nostrand, William E.

Abstract

Cerebral amyloid angiopathy (CAA), a condition characterized by cerebral vascular amyloid accumulation, neuroinflammation, microbleeds, and white matter (WM) degeneration, is a common comorbidity in Alzheimer disease and a prominent contributor to vascular cognitive impairment and dementia. Recently, we reported WM loss in the corpus callosum (CC) in the rTg-DI rat model of CAA. Here, we show that the CC exhibits a much lower CAA burden compared with the adjacent cortex. Using Sequential Window Acquisition of All Theoretical Mass Spectra liquid chromatography coupled with tandem mass spectrometry, we report specific proteomic changes in the CC with emerging WM loss and compare them with the proteome of adjacent cortical tissue in rTg-DI rats. In the CC, annexin A3, heat shock protein β1, and cystatin C were elevated at 4 months (M) before WM loss and also at 12M with evident WM loss. Although annexin A3 and cystatin C were also enhanced in the cortex at 12M, annexin A5 and the leukodystrophy-associated astrocyte proteins megalencephalic leukoencephalopathy with subcortical cysts 1 and GlialCAM were distinctly elevated in the CC. Pathway analysis indicated that neurodegeneration of axons, reflected by reduced expression of myelin and neurofilament proteins, was common to the CC and cortex; activation of Tgfβ1 and F2/thrombin was restricted to the CC. Herein we report new insight into the proteomic changes that accompany WM loss in the CC of rTg-DI rats.

Published
2021
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