Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro
Thesis: M. Eng., Massachusetts Institute of Technology, Department of Biological Engineering, May, 2020
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2020
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| Online Access: | https://hdl.handle.net/1721.1/127885 |
| _version_ | 1826192286610882560 |
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| author | Kamath, Tarun(Tarun Vinod) |
| author2 | Douglas A. Lauffenburger. |
| author_facet | Douglas A. Lauffenburger. Kamath, Tarun(Tarun Vinod) |
| author_sort | Kamath, Tarun(Tarun Vinod) |
| collection | MIT |
| description | Thesis: M. Eng., Massachusetts Institute of Technology, Department of Biological Engineering, May, 2020 |
| first_indexed | 2024-09-23T09:08:53Z |
| format | Thesis |
| id | mit-1721.1/127885 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T09:08:53Z |
| publishDate | 2020 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1278852020-10-09T03:31:47Z Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro Kamath, Tarun(Tarun Vinod) Douglas A. Lauffenburger. Massachusetts Institute of Technology. Department of Biological Engineering. Massachusetts Institute of Technology. Department of Biological Engineering Biological Engineering. Thesis: M. Eng., Massachusetts Institute of Technology, Department of Biological Engineering, May, 2020 Cataloged from PDF version of thesis. Includes bibliographical references (pages. 85-97). Tau neurofibrillary tangles or aggregates are a common neuropathological feature found in a number of neurodegenerative conditions, including Alzheimer's disease. Understanding the kinetics of this aggregate build up, how it varies across patients, and how aggregation might be influenced by intracellular pathways is critical for both a deeper knowledge of these disorders as well as identification of potential therapeutic targets. To this end, I employed an in vitro tau aggregation assay to study the kinetics of tau aggregation as it relates to aggregates in sporadic Alzheimer's disease. I found that the formation of aggregates was a logistic process, with a lag phase, an exponential rise phase, and a plateau phase. Aggregation kinetics varied significantly between different cases of sporadic Alzheimer's disease, paralleling the heterogeneity that is observed in the clinical presentation of Alzheimer's disease. Likewise, I found that inhibition of intracellular pathways of macroautophagy and endosomal microautopahgy heterogeneously increased tau aggregation and changed tau aggregation kinetics, dependent upon the case of Alzheimer's disease. These results inform that tau aggregates vary significantly not just between disorders, but even within disorders, and that protein degradation pathways uniquely process aggregates, perhaps potentiated by further molecular differences in aggregate structure or composition. by Tarun Kamath. M. Eng. M.Eng. Massachusetts Institute of Technology, Department of Biological Engineering 2020-10-08T21:28:47Z 2020-10-08T21:28:47Z 2020 2020 Thesis https://hdl.handle.net/1721.1/127885 1196910130 eng MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided. http://dspace.mit.edu/handle/1721.1/7582 97 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biological Engineering. Kamath, Tarun(Tarun Vinod) Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro |
| title | Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro |
| title_full | Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro |
| title_fullStr | Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro |
| title_full_unstemmed | Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro |
| title_short | Tau aggregation is heterogeneous across cases of sporadic Alzheimer's disease and is influenced by autophagy pathways in vitro |
| title_sort | tau aggregation is heterogeneous across cases of sporadic alzheimer s disease and is influenced by autophagy pathways in vitro |
| topic | Biological Engineering. |
| url | https://hdl.handle.net/1721.1/127885 |
| work_keys_str_mv | AT kamathtaruntarunvinod tauaggregationisheterogeneousacrosscasesofsporadicalzheimersdiseaseandisinfluencedbyautophagypathwaysinvitro |