Student Theses and Dissertations


Dylan Kwart

Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)


Alzheimer’s disease (AD) is the most common cause of dementia worldwide and a leading cause of death in the United States. Rare cases of autosomal dominant familial AD (fAD) result from genetic mutations in three key genes: amyloid precursor protein (APP), and two APP processing-related genes (presenilin-1 (PSEN1), and presenilin-2 (PSEN2)), supporting the theory that altered APP metabolism is a central cause of AD. However, which product of APP metabolism is causal remains a matter of investigation. A probable source of this lack of understanding stems from the poor disease model systems that have been utilized in the field for many years. Recently, advances in human induced pluripotent stem cell (iPSC) technology has enabled the study of uniquely human diseases, such as AD, in human tissue. However, the inability to precisely and efficiently genetically engineer human iPSCs has limited their use in effectively studying monogenic human diseases like fAD.


A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for The degree of Doctor of Philosophy

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