Mechanistic Analysis of AβO-Induced Neurotoxicity and Tau Pathology in an Inducible MC65 Cell Model
Session Number
1
Advisor(s)
Raghad Nowar, Kirsten Viola, William Klein, Northwestern University, Klein Lab
Location
A123
Discipline
Medical and Health Sciences
Start Date
15-4-2026 10:15 AM
End Date
15-4-2026 11:00 AM
Abstract
Alzheimer’s disease is characterized by the buildup of amyloid-β oligomers (AβOs), tau pathology, and eventual neuronal loss. Yet, the mechanisms that link these processes remain incompletely understood. This project looks into whether induction of AβO in MC65 cells drives neurotoxicity through increased tau phosphorylation and other associated cellular stress pathways. The MC65 model allows for intracellular AβO accumulation through withdrawal of tetracycline (-Tet), while tetracycline presence (+Tet) suppresses Aβ production and serves to be a healthy baseline. To look into downstream tau pathology, we use the PHF1 antibody towards immunofluorescence staining to detect phosphorylated tau (p-Tau) under induced and uninduced conditions. Increased PHF1 fluorescence intensity in -Tet cells compared toTet controls indicated elevated tau phosphorylation following the buildup of AβOs. These observations support the link between amyloid toxicity and tau pathology in this model system. Comparably, cell viability and oxidative stress was evaluated to assess the impact of induced toxicity from AβOs. We build a computational model, specifically a pipeline that measures p-Tau intensity per cell, quantifies the proportion of p-Tau positive cells, and relates these measures to cellular health. In short, this work clarifies the relationship of amyloid toxicity and neurodegeneration along with a framework for quantifying cellular relationships.
Mechanistic Analysis of AβO-Induced Neurotoxicity and Tau Pathology in an Inducible MC65 Cell Model
A123
Alzheimer’s disease is characterized by the buildup of amyloid-β oligomers (AβOs), tau pathology, and eventual neuronal loss. Yet, the mechanisms that link these processes remain incompletely understood. This project looks into whether induction of AβO in MC65 cells drives neurotoxicity through increased tau phosphorylation and other associated cellular stress pathways. The MC65 model allows for intracellular AβO accumulation through withdrawal of tetracycline (-Tet), while tetracycline presence (+Tet) suppresses Aβ production and serves to be a healthy baseline. To look into downstream tau pathology, we use the PHF1 antibody towards immunofluorescence staining to detect phosphorylated tau (p-Tau) under induced and uninduced conditions. Increased PHF1 fluorescence intensity in -Tet cells compared toTet controls indicated elevated tau phosphorylation following the buildup of AβOs. These observations support the link between amyloid toxicity and tau pathology in this model system. Comparably, cell viability and oxidative stress was evaluated to assess the impact of induced toxicity from AβOs. We build a computational model, specifically a pipeline that measures p-Tau intensity per cell, quantifies the proportion of p-Tau positive cells, and relates these measures to cellular health. In short, this work clarifies the relationship of amyloid toxicity and neurodegeneration along with a framework for quantifying cellular relationships.