Abstract
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.
Highlights
Parkinson’s disease (PD) is expected to affect between 8.7 and 9.3 million people globally by 20301, but the cause or causes of this neurodegenerative disease remain relatively unknown
The anterior olfactory nucleus is the main site of aggregated alpha-synuclein pathology in the PD olfactory bulb[9, 51], iron was present at very low levels in this region
Copper was low in the anterior olfactory nucleus, but zinc was relatively high in this secondary olfactory processing region
Summary
Parkinson’s disease (PD) is expected to affect between 8.7 and 9.3 million people globally by 20301, but the cause or causes of this neurodegenerative disease remain relatively unknown. 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[20,21,22] These metals have been implicated in olfaction: increased olfactory bulb iron correlates with hyposmia in humans[23], while intranasal zinc can cause anosmia in humans and animals[24,25,26,27], and intranasal copper reduces olfaction in fish[28,29,30]. We present evidence that metal concentrations are altered in the PD olfactory bulb and tract, and show for the first time by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) the localized patterns of iron, zinc, and copper in the human olfactory bulb, anterior olfactory nucleus, and olfactory tract (For schematic of experimental setup see Fig. 1)
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