Olfactory impairment and pathology in neurodegenerative disorders with brain iron accumulation

Dziewulska, Dorota; Doi, Hiroshi; Fasano, Alfonso; Erro, Roberto; Fatehi, Farzad; Fekete, Róbert; Gatto, Emilia; Pablos, Emilio González; Lehn, Alexander; Miyajima, Hiroaki; Piperno, Alberto; Pellechia, Maria Teresa; Wu, Yih‐Ru; Yoshida, Katsumi; Zarruk, Juan G.; Jiang, Shan; Schrag, Anette; McNeill, Alisdair

doi:10.1007/s00401-013-1136-3

Cited by 9 publications

(2 citation statements)

References 4 publications

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“…However, this increase in iron and sodium may be clinically important in producing the hyposmia and anosmia that occur in PD. Neurodegeneration disorders with brain iron accumulation result in increased olfactory bulb iron and decreased olfactory ability 23 , and iron is known to be essential for the function of enzymes that are important in normal olfaction, such as neuronal nitric oxide synthase and hydroxyanthranilic acid 77 . Sodium also plays a role in olfaction: voltage-gated sodium channels are necessary for odor perception in mice, fruit flies, and humans 78 , 79 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, elevated levels of iron, copper 17 , and zinc 18 , 19 cause aggregation of alpha-synuclein in vitro , and are taken up into the olfactory bulbs of rodents following intranasal exposure 20 – 22 . These metals have also been implicated in olfaction: increased olfactory bulb iron correlates with hyposmia in humans 23 , while intranasal zinc can cause anosmia in humans and animals 24 – 27 , and intranasal copper reduces olfaction in fish 28 – 30 .…”

Section: Introductionmentioning

confidence: 99%

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Metal concentrations and distributions in the human olfactory bulb in Parkinson’s disease

Gardner

Dieriks

Cameron

et al. 2017

Sci Rep

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In Parkinson’s disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p < 0.05) and sodium (p < 0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation. Zinc was high in these regions, and free zinc was detected in Lewy bodies, mitochondria, and lipofuscin of cells in the anterior olfactory nucleus. Increased iron and sodium in the human PD olfactory bulb may relate to the loss of olfactory function. In contrast, colocalization of free zinc and alpha-synuclein in the anterior olfactory nucleus implicate zinc in PD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metal concentrations and distributions in the human olfactory bulb in Parkinson’s disease

Gardner

Dieriks

Cameron

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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Olfactory bulb involvement in neurodegenerative diseases

2014

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Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Parkinson's disease and other synucleinopathies, Alzheimer's disease (AD), and mild cognitive impairment heralding its progression to dementia. The neuropathologic changes of olfactory dysfunction in neurodegenerative diseases may involve the olfactory epithelium, olfactory bulb/tract, primary olfactory cortices, and their secondary targets. Olfactory dysfunction is related to deposition of pathological proteins, α-synuclein, hyperphosphorylated tau protein, and neurofilament protein in these areas, featured by neurofibrillary tangles, Lewy bodies and neurites inducing a complex cascade of molecular processes including oxidative damage, neuroinflammation, and cytosolic disruption of cellular processes leading to cell death. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with severe anosmia. Recent studies of olfactory dysfunction have focused its potential as an early biomarker for the diagnosis of neurodegenerative disorders and their disease progression. Here, we summarize the current knowledge on neuropathological and pathophysiological changes of the olfactory system in the most frequent neurodegenerative diseases, in particular AD and synucleinopathies. We also present neuropathological findings in the olfactory bulb and tract in a large autopsy cohort (n = 536, 57.8 % female, mean age 81.3 years). The severity of olfactory bulb HPτ, Aβ, and αSyn pathology correlated and increased significantly (P < 0.001) with increasing neuritic Braak stages, Thal Aβ phases, and cerebral Lewy body pathology, respectively. Hence, further studies are warranted to investigate the potential role of olfactory biopsies (possibly restricted to the olfactory epithelium) in the diagnostic process of neurodegenerative diseases in particular in clinical drug trials to identify subjects showing early, preclinical stages of neurodegeneration and to stratify clinically impaired cohorts according to the underlying cerebral neuropathology.

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Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update. II. Hyperkinetic disorders

Jellinger¹

2019

J Neural Transm

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Olfactory impairment and pathology in neurodegenerative disorders with brain iron accumulation

Cited by 9 publications

References 4 publications

Metal concentrations and distributions in the human olfactory bulb in Parkinson’s disease

Metal concentrations and distributions in the human olfactory bulb in Parkinson’s disease

Olfactory bulb involvement in neurodegenerative diseases

Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update. II. Hyperkinetic disorders

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