Prog Neuropsychopharmacol Biol Psychiatry

. 2023 Nov 28:110903.

doi: 10.1016/j.pnpbp.2023.110903. Online ahead of print.

Changes in iron load in specific brain areas lead to neurodegenerative diseases of the central nervous system

Xinghao Wang ¹, Zaimin Zhu ², Jing Sun ¹, Li Jia ¹, Linkun Cai ³, Qian Chen ¹, Wenbo Yang ¹, Yiling Wang ¹, Yufan Zhang ¹, Sihui Guo ¹, Wenjuan Liu ⁴, Zhenghan Yang ¹, Pengfei Zhao ¹, Zhenchang Wang ⁵, Han Lv ⁶

Affiliations expand

• PMID: 38036035

DOI: 10.1016/j.pnpbp.2023.110903

Abstract

The causes of neurodegenerative diseases remain largely elusive, increasing their personal and societal impacts. To reveal the causal effects of iron load on Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis and multiple sclerosis, we used Mendelian randomisation and brain imaging data from a UK Biobank genome-wide association study of 39,691 brain imaging samples (predominantly of European origin). Using susceptibility-weighted images, which reflect iron load, we analysed genetically significant brain regions. Inverse variance weighting was used as the main estimate, while MR Egger and weighted median were used to detect heterogeneity and pleiotropy. Nine clear associations were obtained. For AD and PD, an increased iron load was causative: the right pallidum for AD and the right caudate, left caudate and right accumbens for PD. However, a reduced iron load was identified in the right and left caudate for multiple sclerosis, the bilateral hippocampus for mixed vascular dementia and the left thalamus and bilateral accumbens for subcortical vascular dementia. Thus, changes in iron load in different brain regions have causal effects on neurodegenerative diseases. Our results are crucial for understanding the pathogenesis and investigating the treatment of these diseases.