Human Induced Pluripotent Stem Cells Derived from A Patient with Sporadic Alzheimer’s Disease Exhibit Altered Neuronal Proliferative Capacity

We generated two hiPSC clones from a patient with sporadic late-onset Alzheimer’s disease (AD-iPSCs), which expressed typical undifferentiated markers and passed standard pluripotency assays. Genome-wide microarray analysis revealed that AD-iPSCs were highly similar to control hiPSCs and hESCs, albeit with some noticeable differences in few genes, viz.: DNAJC15, GRPR, NAIP and SNORD116-18. Several other biomarkers were differentially expressed in AD-iPSC clones which have been implicated in memory impairment and AD. Furthermore, well characterized familial (APP, PSEN1, PSEN2) and non-familial (A2M, APOE, GAP43, MAOA, MPO, PLAT, PLAU, SORL1, SNCA) AD-associated genes exhibited different expression patterns but were largely reset upon reprogramming into a pluripotent state. AD-iPSC clones could efficiently form neuroprogenitors via rosette formation but one of the two AD-iPSC clones exhibited a lower proliferation rate as determined by EdU incorporation assays. Further analysis revealed this lower proliferation was due to an increase in apoptotic gene expression. The data suggest that hiPSCs could be good candidates for AD modeling and may represent an in vitro alternative to studying disease mechanisms, drug discovery and toxicological studies. Further studies are required to ascertain the significance of the resetting of disease specific genes caused by reprogramming as seen in this study.