Xenografted human iPSC-derived neurons with the familial Alzheimer's disease APP^V717I mutation reveal dysregulated transcriptome signatures linked to synaptic function and implicate LINGO2 as a disease signaling mediator.

ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia, and disease mechanisms are still not fully understood. Here, we explored pathological changes in human induced pluripotent stem cell (iPSC)-derived neurons carrying the familial AD APP^V717I mutation after cell injection into the mouse forebrain. APP^V717I mutant iPSCs and isogenic controls were differentiated into neurons revealing enhanced Aβ₄₂ production, elevated phospho-tau, and impaired neurite outgrowth in APP^V717I neurons. Two months after transplantation, APP^V717I and control neural cells showed robust engraftment but at 12 months post-injection, APP^V717I grafts were smaller and demonstrated impaired neurite outgrowth compared to controls, while plaque and

SUBMITTER: Qu W 

PROVIDER: S-EPMC11199265 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature