Related Experiment Video
Updated: Jun 26, 2026
08:29
Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans
Published on: December 18, 2016
13.9K
Genetic Markers of Postmortem Brain Iron
Marilyn C Cornelis1, Amir Fazlollahi2,3, 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.
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.
More Related Videos
Related Concept Videos
02:30Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:16Necrosis
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
01:28Human Genetics
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...