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Examine phenotypic and pharmacological data from a patient-derived iPSC panel modeling sporadic Alzheimer's disease across neurons, astrocytes, and a tri-culture system.
- AD patient-derived excitatory neurons showed statistically higher pTau/Tau and Aβ42/Aβ40 ratios than healthy controls at week 6 post-differentiation, with p<0.007 and p<0.05 respectively.
- GSK3β inhibitor SAR502250 reduced pTau levels across AD and healthy neuronal lines, though response was donor-dependent; coding variants in ABCA1 may account for differential sensitivity in AD lines.
- AD patient-derived astrocytes showed a higher proportion of fibroblast-like morphology compared to healthy donor astrocytes, a phenotype associated with an inflammatory astrocyte state.
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