Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer's disease patients - ScienceDirect

Stem Cell Research

Julian H. Birnbaum¹ 

关键词: Alzheimer';    s disease;    Induced pluripotent stem cells;    Induced neuronal cells;    Sporadic AD;    Mitochondria;    Aβ;    AD;    Alzheimer';    s disease;    CSF;    cerebrospinal fluid;    FAD;    familial Alzheimer';    s disease;    GWAS;    genome-wide association study;    HCS;    healthy control subject;    iN cell;    induced neuronal cell;    iPSC;    induced pluripotent stem cell;    Oxphos;    oxidative phosphorylation chain;    PiB;    Pittsburgh compound B;    SAD;    sporadic Alzheimer';    s disease;    ROS;    reactive oxygen species;   

DOI  :  10.1016/j.scr.2018.01.019

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and increased production of reactive oxygen species (ROS) has been described in postmortem brain samples and animal models. However, these observations were made at a late stage of disease and the inability to examine an early, presymptomatic phase in human neurons impeded our understanding of cause or consequence of mitochondrial dysfunction in AD. We used human induced pluripotent stem cell-derived neuronal cells (iN cells) from sporadic AD (SAD) patients and healthy control subjects (HCS) to show aberrant mitochondrial function in patient-derived cells. We observed that neuronal cultures from some patients produced more ROS and displayed higher levels of DNA damage. Furthermore, patient-derived cells showed increased levels of oxidative phosphorylation chain complexes, whereas mitochondrial fission and fusion proteins were not affected. Surprisingly, these effects neither correlated with Aβ nor phosphorylated and total tau levels. Synaptic protein levels were also unaffected in SAD iN cells. The results of this study give new insights into constitutional metabolic changes in neurons from subjects prone to develop Alzheimer's pathology. They suggest that increased ROS production may have an integral role in the development of sporadic AD prior to the appearance of amyloid and tau pathology.

【 授权许可】

Unknown