TY  - GEN
N2  - Clathrin mediated endocytosis (CME) is emerging as a critical player in the development and progression of AD in multiple brain cell types. CME is an important intersection between early neuronal dysfunction via Aβ1-42 accumulation and downstream effects that contribute to neuronal viability, such as synaptic vesicle recycling deficits and disruption of AMPAR regulation. Not only is Aβ1-42 produced following CME of APP, but internalization of multiple forms of extracellular Aβ1-42 contribute to downstream neuronal pathology. In astrocytes and microglia, which are heavily involved in clearance of extracellular Aβ1-42 in the brain, CME disruptions reduce internalization of Aβ1-42. Ultimately, CME appears to be involved in dysfunction in multiple cell types across early and late stages of AD. Thus, elucidating the mechanisms of CME and how their disruption is related to AD pathogenesis or neuroprotection in each brain cell type would both lead to a better understanding of AD mechanisms and potentially point to novel targets for the treatment or prevention of AD. In this dissertation work, I have begun to assess CME in the context of AD, using human post-mortem samples and the 5xFAD AD mouse model.
DO  - 10.6083/bpxhc42886
DO  - doi
AB  - Clathrin mediated endocytosis (CME) is emerging as a critical player in the development and progression of AD in multiple brain cell types. CME is an important intersection between early neuronal dysfunction via Aβ1-42 accumulation and downstream effects that contribute to neuronal viability, such as synaptic vesicle recycling deficits and disruption of AMPAR regulation. Not only is Aβ1-42 produced following CME of APP, but internalization of multiple forms of extracellular Aβ1-42 contribute to downstream neuronal pathology. In astrocytes and microglia, which are heavily involved in clearance of extracellular Aβ1-42 in the brain, CME disruptions reduce internalization of Aβ1-42. Ultimately, CME appears to be involved in dysfunction in multiple cell types across early and late stages of AD. Thus, elucidating the mechanisms of CME and how their disruption is related to AD pathogenesis or neuroprotection in each brain cell type would both lead to a better understanding of AD mechanisms and potentially point to novel targets for the treatment or prevention of AD. In this dissertation work, I have begun to assess CME in the context of AD, using human post-mortem samples and the 5xFAD AD mouse model.
AD  - Oregon Health and Science University
T1  - Clathrin mediated endocytosis in Alzheimer's Disease: using biomarkers to uncover disease mechanism
ED  - Saugstad, Julie
ED  - Sandau, Ursula
ED  - Copenhaver, Philip
ED  - Monk, Kelly
ED  - Mishra, Anusha
ED  - Baltan, Selva
ED  - Academic advisor
ED  - Co-Mentor
ED  - Committee chair
ED  - Committee member
ED  - Committee member
ED  - Committee member
DA  - 2023-11-28
AU  - Smith, Sierra Jaye
L1  - https://digitalcollections.ohsu.edu/record/42886/files/Smith.Sierra.2024.pdf
PB  - Oregon Health and Science University
LA  - eng
PY  - 2023-11-28
ID  - 42886
L4  - https://digitalcollections.ohsu.edu/record/42886/files/Smith.Sierra.2024.pdf
KW  - Alzheimer Disease
KW  - Models, Animal
KW  - Clathrin
KW  - Endocytosis
KW  - clathrin mediated endocytosis
KW  - intersectin 1
TI  - Clathrin mediated endocytosis in Alzheimer's Disease: using biomarkers to uncover disease mechanism
Y1  - 2023-11-28
L2  - https://digitalcollections.ohsu.edu/record/42886/files/Smith.Sierra.2024.pdf
LK  - https://digitalcollections.ohsu.edu/record/42886/files/Smith.Sierra.2024.pdf
UR  - https://digitalcollections.ohsu.edu/record/42886/files/Smith.Sierra.2024.pdf
ER  -