Abstract #3901

Insights into neurodegeneration in Alzheimer’s disease from regional Aβ aggregation, iron level, and gene expression in postmortem human brain

Junye Yao^1,2, Zhenghao Li³, Zihan Zhou^1,4, Aimin Bao⁵, Jianhui Zhong⁶, Hongjiang Wei³, and Hongjian He^1,7,8

¹Center for Brain Imaging Science and Technology, Zhejiang University, Hangzhou, China, ²College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China, ³School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ⁴Stanford University Graduate School of Education, Department of Radiology, Standford University, Stanford, CA, United States, ⁵National Human Brain Bank for Health and Disease, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China, ⁶Department of Imaging Sciences, University of Rochester, Rochester, NY, United States, ⁷School of Physics, Zhejiang University, Hangzhou, China, ⁸State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, China

Synopsis

Keywords: Alzheimer's Disease, Alzheimer's Disease

Motivation: Quantifying Aβ in patients with Alzheimer's disease poses a challenge due to the colocalization of Aβ accumulation and iron deposition.

Goal(s): Our goal was to simultaneously quantify Aβ and iron in ex-vivo human brains affected by AD.

Approach: We used a novel subvoxel QSM method to measure Aβ and iron levels. The gene transcriptomic profiles were further investigated using PLS and ontological analysis.

Results: Regions with higher diamagnetic and paramagnetic susceptibility were found higher levels of gene expression relating to the protein modification process and metal ion binding, as well as a relative abundance of exCA and glutamatergic neurons.

Impact: The quantification of diamagnetic and paramagnetic susceptibility via APART-QSM can offer valuable insights into regional-specific vulnerabilities in Alzheimer’s disease, particularly those related to Aβ aggregation and iron accumulation. This can aid clinicians to better find therapeutic targets.

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