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Related Experiment Video

Updated: Jun 26, 2026

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

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Published on: December 18, 2016

Genetic Markers of Postmortem Brain Iron.

Marilyn C Cornelis¹, Amir Fazlollahi^2,3, David A Bennett⁴

¹Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Journal of Neurochemistry

|February 7, 2025

Summary

Brain iron dysregulation is linked to neurodegenerative diseases. This study identified novel genetic factors influencing brain iron levels, some connected to cellular transport and mitochondrial function, offering new insights into brain health.

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Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry CE-ICP-MS for Quantification of Iron Redox Species FeII, FeIII

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Published on: May 23, 2025

Area of Science:

Neuroscience
Genetics
Biochemistry

Background:

Iron (Fe) dyshomeostasis in the brain is a known factor in neurodegenerative diseases.
Genome-wide association studies (GWAS) have previously identified genetic loci associated with peripheral iron levels.

Purpose of the Study:

To conduct the first GWAS on postmortem brain iron levels.
To identify novel genetic loci and pathways influencing brain iron accumulation.
To investigate the overlap between genetic determinants of brain and peripheral iron levels.

Main Methods:

Performed GWAS on inductively coupled plasma mass spectrometry measures of postmortem brain iron in 635 participants.
Measured 16 single nucleotide polymorphisms (SNPs) associated with brain iron.
Followed up promising SNPs for replication in published GWAS of blood, spleen, and brain imaging iron traits.
Conducted targeted cortical transcriptomic and epigenetic analyses of candidate genes.

Main Results:

Identified 98 SNPs associated with postmortem brain iron, with 16 reaching genome-wide significance.
Novel loci were linked to endoplasmic reticulum-Golgi trafficking, heparan sulfate, and coenzyme A pathways.
Replicated previously published iron loci associated with cellular and systemic iron regulation.
Identified novel loci (BMAL, COQ5, SLC25A11) and replicated prior loci (PINK1, PPIF, LONP1) supporting roles for circadian rhythms and mitochondria in iron regulation.

Conclusions:

Novel genetic loci associated with brain iron accumulation, potentially relevant to neurodegeneration, were identified.
Findings suggest pathways beyond direct iron regulation, including cellular trafficking and mitochondrial function, are involved in brain iron homeostasis.
Replication of some peripheral iron loci indicates shared genetic underpinnings between brain and systemic iron regulation.