This study investigates the use of induced pluripotent stem cells (iPSCs) to model sporadic and familial Alzheimer's disease. The researchers reprogrammed primary fibroblasts from patients with familial Alzheimer's disease (caused by a duplication of the amyloid-β precursor protein gene, APPDp) and two patients with sporadic Alzheimer's disease (sAD1 and sAD2) into iPSC lines. Neurons were purified from these iPSC lines using fluorescence-activated cell sorting and characterized for electrophysiological activity and synaptic function. The results showed that neurons from APPDp and sAD2 patients exhibited significantly higher levels of pathological markers such as amyloid-β(1–40), phospho-tau(Thr 231), and active glycogen synthase kinase-3β (aGSK-3β) compared to controls. Treatment with β-secretase inhibitors reduced these levels, suggesting a direct relationship between APP processing and tau phosphorylation. Additionally, neurons from sAD2 patients showed phenotypes similar to those seen in familial Alzheimer's disease samples. The study demonstrates that iPSC technology can be used to observe Alzheimer's disease phenotypes, even though overt disease may take decades to manifest in patients.This study investigates the use of induced pluripotent stem cells (iPSCs) to model sporadic and familial Alzheimer's disease. The researchers reprogrammed primary fibroblasts from patients with familial Alzheimer's disease (caused by a duplication of the amyloid-β precursor protein gene, APPDp) and two patients with sporadic Alzheimer's disease (sAD1 and sAD2) into iPSC lines. Neurons were purified from these iPSC lines using fluorescence-activated cell sorting and characterized for electrophysiological activity and synaptic function. The results showed that neurons from APPDp and sAD2 patients exhibited significantly higher levels of pathological markers such as amyloid-β(1–40), phospho-tau(Thr 231), and active glycogen synthase kinase-3β (aGSK-3β) compared to controls. Treatment with β-secretase inhibitors reduced these levels, suggesting a direct relationship between APP processing and tau phosphorylation. Additionally, neurons from sAD2 patients showed phenotypes similar to those seen in familial Alzheimer's disease samples. The study demonstrates that iPSC technology can be used to observe Alzheimer's disease phenotypes, even though overt disease may take decades to manifest in patients.