基本信息
浏览量:265
职业迁徙
个人简介
Research Narrative
My lab aims to understand cerebral amyloid angiopathy (CAA), using mouse models and human tissue. In this disease, the peptide Aβ deposits in the walls of blood vessels and is associated with risk of hemorrhage (‘lobar hemorrhages’). This peptide is the same material that forms the plaques of Alzheimer disease, and nearly all patients with Alzheimer disease have pathologic evidence of CAA as well. CAA also occurs in the absence of histologic evidence of Alzheimer disease, and can present with hemorrhages or with cognitive changes. In clinicopathologic studies, we have found that this latter presentation is associated with the presence of an inflammatory response, often containing giant cells. This subset of patients can have dramatic recoveries of cognitive function after immunosuppressive therapy.
We are interested in the sequence of events by which Aβ is deposited in blood vessels, what factors determine the distribution of involvement, what the consequences are for the cells of the vessel and how this material can respond to therapeutic interventions that have been shown to alter Aβ deposits in the brain (immunotherapy, gamma-secretase inhibitors). Current topics of particular interest involve the timing of oxidative stress induction by CAA, expression of matrix degrading enzymes such as MMP-9 and induction of apoptosis in vascular smooth muscle cells. We use serial in vivo multiphoton imaging with specific probes for these various processes and link the spatial and temporal distribution of the pathologic changes with the development of CAA. We complement these studies with immunohistochemistry, image reconstruction and laser capture microdissection to define alterations in gene expression that occur in smooth muscle cells in the proximity of amyloid deposits of CAA. Finally, our observations in mouse models of CAA can be validated through the use of human autopsy tissue, collected through the Massachusetts Alzheimer Disease Research Center Neuropathology Core.
I also work with a range of collaborators to understand the relationship between neuropathologic findings in the setting of disease – including Alzheimer disease, Parkinson disease, Amyotrophic Lateral Sclerosis and others – and other biochemical or functional markers of disease. These studies include advancing imaging methods (DTI, OCT and others) as well as various genetic studies (deep sequencing as well as GWAS), cell biology and structural biology.
My lab aims to understand cerebral amyloid angiopathy (CAA), using mouse models and human tissue. In this disease, the peptide Aβ deposits in the walls of blood vessels and is associated with risk of hemorrhage (‘lobar hemorrhages’). This peptide is the same material that forms the plaques of Alzheimer disease, and nearly all patients with Alzheimer disease have pathologic evidence of CAA as well. CAA also occurs in the absence of histologic evidence of Alzheimer disease, and can present with hemorrhages or with cognitive changes. In clinicopathologic studies, we have found that this latter presentation is associated with the presence of an inflammatory response, often containing giant cells. This subset of patients can have dramatic recoveries of cognitive function after immunosuppressive therapy.
We are interested in the sequence of events by which Aβ is deposited in blood vessels, what factors determine the distribution of involvement, what the consequences are for the cells of the vessel and how this material can respond to therapeutic interventions that have been shown to alter Aβ deposits in the brain (immunotherapy, gamma-secretase inhibitors). Current topics of particular interest involve the timing of oxidative stress induction by CAA, expression of matrix degrading enzymes such as MMP-9 and induction of apoptosis in vascular smooth muscle cells. We use serial in vivo multiphoton imaging with specific probes for these various processes and link the spatial and temporal distribution of the pathologic changes with the development of CAA. We complement these studies with immunohistochemistry, image reconstruction and laser capture microdissection to define alterations in gene expression that occur in smooth muscle cells in the proximity of amyloid deposits of CAA. Finally, our observations in mouse models of CAA can be validated through the use of human autopsy tissue, collected through the Massachusetts Alzheimer Disease Research Center Neuropathology Core.
I also work with a range of collaborators to understand the relationship between neuropathologic findings in the setting of disease – including Alzheimer disease, Parkinson disease, Amyotrophic Lateral Sclerosis and others – and other biochemical or functional markers of disease. These studies include advancing imaging methods (DTI, OCT and others) as well as various genetic studies (deep sequencing as well as GWAS), cell biology and structural biology.
研究兴趣
论文共 572 篇作者统计合作学者相似作者
按年份排序按引用量排序主题筛选期刊级别筛选合作者筛选合作机构筛选
时间
引用量
主题
期刊级别
合作者
合作机构
Astrid Wachter,Maya E. Woodbury, Sylvia Lombardo, Aicha Abdourahman, Carolin Wuest, Emily McGlame, Timothy Pastika,Joseph Tamm, Nandini Romanul,Kiran Yanamandra,Rachel Bennett,Gen Lin,
Acta Neuropathologicano. 1 (2024): 1-20
JOURNAL OF COMPARATIVE NEUROLOGYno. 3 (2024): e25604-e25604
Astrid Wachter,Maya E. Woodbury, Sylvia Lombardo, Aicha Abdourahman, Carolin Wuest, Emily Mcglame, Timothy Pastika,Joseph Tamm, Nandini Romanul,Kiran Yanamandra, Rachel Bennett,Gen Lin,
ACTA NEUROPATHOLOGICAno. 1 (2024)
David G Amaral,Jean Augustinack,Helen Barbas,Matthew Frosch, John Gabrieli, Jennifer Luebke,Pasko Rakic,Douglas Rosene,Richard J Rushmore
Hippocampus (2024)
引用0浏览0WOS引用
0
0
Elie Massaad, William J Smith,Joseph Bradley, Eric Esposito,Mihir Gupta, Evan Burns, Ryan Burns, José K Velarde, Inka K Berglar,Rajiv Gupta,Maria Martinez-Lage,Jorg Dietrich,
Alain Ndayisaba, Ariana T. Pitaro, Andrew S. Willett, Kristie A. Jones,Claudio Melo de Gusmao,Abby L. Olsen, Jisoo Kim,Eero Rissanen, Jared K. Woods,Sharan R. Srinivasan, Anna Nagy, Amanda Nagy,
The Cerebellumno. 1 (2024): 31-51
Harshvardhan Gazula,Henry F J Tregidgo, Benjamin Billot,Yael Balbastre, Jonathan William-Ramirez, Rogeny Herisse, Lucas J Deden-Binder,Adrià Casamitjana,Erica J Melief,Caitlin S Latimer,Mitchell D Kilgore, Mark Montine,
bioRxiv : the preprint server for biology (2024)
Yi Gong,Fiza Laheji,Anna Berenson, Yedda Li,Ann Moser,April Qian,Matthew Frosch,Reza Sadjadi, Ryan Hahn,Casey A. Maguire,Florian Eichler
ANNALS OF NEUROLOGYno. 3 (2024): 442-458
加载更多
作者统计
合作学者
合作机构
D-Core
- 合作者
- 学生
- 导师
数据免责声明
页面数据均来自互联网公开来源、合作出版商和通过AI技术自动分析结果,我们不对页面数据的有效性、准确性、正确性、可靠性、完整性和及时性做出任何承诺和保证。若有疑问,可以通过电子邮件方式联系我们:report@aminer.cn