1. Academic Validation
  2. Increased GABAergic development in iPSC-derived neurons from patients with sporadic Alzheimer's disease

Increased GABAergic development in iPSC-derived neurons from patients with sporadic Alzheimer's disease

  • Neurosci Lett. 2020 Sep 14;735:135208. doi: 10.1016/j.neulet.2020.135208.
Yueyu Tang 1 Yingying Han 1 Hongxiang Yu 1 Bei Zhang 2 Gang Li 3
Affiliations

Affiliations

  • 1 Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, 200123, China.
  • 2 Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, 200123, China. Electronic address: zhangbei0227@163.com.
  • 3 Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, 1800 Yuntai Road, Shanghai, 200123, China. Electronic address: ligang@tongji.edu.cn.
Abstract

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and the underlying molecular mechanisms of this neurodegenerative disorder are still unclear. γ-Aminobutyric acid (GABA) neurons play an essential role in the excitatory/inhibitory (E/I) balance in the brain, and the GABAergic system may contribute to the pathogenesis of AD. We used human induced pluripotent stem cells (iPSCs) generated from sporadic AD (SAD) patients to analyze the phenotype and transcriptional profiles of SAD iPSC-derived neural cells. We observed reduced neurogenesis and increased astrogenesis in SAD neural differentiation. We discovered elevated levels of GABA, glutamate decarboxylase 67 (GAD67), and vesicular GABA transporter (vGAT) in SAD neurons that indicated increased GABAergic development. Gene expression profiling of SAD neural cultures showed upregulation of the GABAergic signaling pathway and downregulation of the neurogenesis pathway. We presumed that the GABAergic transmission system might be enhanced in SAD neurons, as an early pathological change of SAD, which provides a novel target and new direction for the development of more effective therapeutic strategies.

Keywords

Alzheimer’s disease; Induced pluripotent stem cells; Neurogenesis; Sporadic; γ-Aminobutyric acid.

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