Ultrastructural Evidence of Altered Dendritic Morphology in the Prefrontal Cortex of Alzheimer's Model Rats
Jinyue Guo1,2 · Jing Liu1 · Yanchao Zhang1,3 · Jiazheng Liu1 · Hao Zhai1,4 · Linlin Li1 · Hua Han1,3
1 State Key Laboratory of Brain Cognition and Brain‑inspired Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
2 School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing 101408, China
3 School of Future Technology, University of Chinese Academy of Sciences, Beijing 101408, China
4 Department of Connectomics, Max Planck Institute for Brain Research, 60438 Frankfurt, Germany
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder with synaptic pathology as a core theme in aging-related research. Conventional imaging and limited tools fail to resolve AD-relevant nanoscale structures. Here, we present an automated pipeline integrating volume electron microscopy (vEM) with deep learning to analyze synapses and subcellular components, enabling 3D reconstruction of neuronal architecture in ~130,000 μm3 of rat prefrontal cortex (PFC). Preliminary results from small animal samples show that, vs. controls, AD rats have fewer mushroom spines but more thin/stubby spines. Synaptic and mitochondrial surface area/volume are reduced, with increased multi-contact synapses. These findings suggest mature spine loss with compensatory morphological changes, potentially impairing dendritic integration. Our method highlights the potential of vEM-deep learning integration for detailed ultrastructural quantification in neurodegenerative models, laying a foundation for future large-sample pathological studies.
Keywords
Alzheimer’s disease; Synapse; Volume electron microscope; Dendritic spine; Subcellular ultrastructure
