Disruption of cerebral
iron regulation appears to have a role in aging and in the pathogenesis of various
neurodegenerative disorders. Possible unfavorable impacts of
iron accumulation include
reactive oxygen species generation, induction of ferroptosis, and acceleration of inflammatory changes. Whole-brain
iron-sensitive magnetic resonance imaging (MRI) techniques allow the examination of macroscopic patterns of brain
iron deposits in vivo, while modern analytical methods ex vivo enable the determination of
metal-specific content inside individual cell-types, sometimes also within specific cellular compartments. The present review summarizes the whole brain, cellular, and subcellular patterns of
iron accumulation in
neurodegenerative diseases of genetic and sporadic origin. We also provide an update on mechanisms,
biomarkers, and effects of brain
iron accumulation in these disorders, focusing on recent publications. In
Parkinson's disease,
Friedreich's disease, and several disorders within the neurodegeneration with brain
iron accumulation group, there is a focal
siderosis, typically in regions with the most pronounced neuropathological changes. The second group of disorders including
multiple sclerosis,
Alzheimer's disease, and
amyotrophic lateral sclerosis shows
iron accumulation in the globus pallidus, caudate, and putamen, and in specific cortical regions. Yet, other disorders such as
aceruloplasminemia,
neuroferritinopathy, or
Wilson disease manifest with diffuse
iron accumulation in the deep gray matter in a pattern comparable to or even more extensive than that observed during normal aging. On the microscopic level, brain
iron deposits are present mostly in dystrophic microglia variably accompanied by
iron-laden macrophages and in astrocytes, implicating a role of inflammatory changes and blood-brain barrier disturbance in
iron accumulation. Options and potential benefits of
iron reducing strategies in neurodegeneration are discussed. Future research investigating whether
genetic predispositions play a role in brain Fe accumulation is necessary. If confirmed, the prevention of further brain Fe uptake in individuals at risk may be key for preventing
neurodegenerative disorders.