Application Note

< Previous         Next >  
Synaptic degeneration in the prefrontal cortex of a rat AD model revealed by volume electron microscopy
Yi Jiang1,2,† , Linlin Li1,† , Keliang Pang3,4,† , Jiazheng Liu1,5 , Bohao Chen1,2 , Jingbin Yuan1,2 , Lijun Shen1 , Xi Chen1 , Bai Lu3,4 , Hua Han1,5,6,*
1National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
2School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 101408, China
3School of Pharmaceutical Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China
4Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
5School of Future Technology, University of Chinese Academy of Sciences, Beijing 101408, China
6Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
These authors contributed equally to this work
*Correspondence to:Hua Han ,
J Mol Cell Biol, Volume 14, Issue 3, March 2022, mjac012,

Alzheimer's disease (AD), a neurodegenerative disease, is identified as the most common cause of dementia (Goedert and Spillantini, 2006). Typical symptoms of AD in neuropathology are closely associated with changes in synapses and neurons (Serrano-Pozo et al., 2011). The prefrontal cortex (PFC) plays a crucial role in executive function, controlling the highest level of cognitive and emotional processes, and is also vulnerable to neurodegeneration in AD (Salat et al., 2001). While synaptic degeneration is believed to underlie the progressive decline of cognition in AD, specific changes in synaptic structures relevant to AD remain elusive due to a shortage of quantitative tools. Synaptic dysfunction, while key to AD pathophysiology, is difficult to monitor and study in human AD patients. The existing technologies, such as cerebrospinal fluid or blood biomarkers, magnetic resonance imaging, and positron emission tomography, can only indirectly infer synaptic changes in the brain. Thus, it is critical to have an animal model that resembles closely human AD. The newly developed AD rat model, the amyloid precursor protein (App) knock-in rat line harboring Swedish–Beyreuther/Iberian−Arctic mutations (homozygous AppNL-G-F rat), offers a great opportunity (Pang et al., 2021). Electron microscopy (EM) has been the method of choice to study the ultrastructure of synapses. While allowing magnification of images by a million times, this conventional EM provides snapshots, rather than quantitative measures, of ultrastructural details of synapses. With the development of automated tape-collecting ultramicrotome (ATUM; Baena et al., 2019) and artificial intelligence (AI)-assisted 3D reconstruction of scanning electron microscopy (SEM) images (Motta et al., 2019), it is now possible to quantitatively characterize morphological features of synapses and dendrites in detail.