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Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain

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Abstract

Both apolipoprotein E (apoE) and zinc are involved in amyloid β (Aβ) aggregation and deposition, in the hallmark neuropathology of Alzheimer’s disease (AD). Recent studies have suggested that interaction of apoE with metal ions may accelerate amyloidogenesis in the brain. Here we examined the impact of apoE deficiency on the histochemically reactive zinc pool in the brains of apoE knockout mice. While there was no change in total contents of metals (zinc, copper, and iron), the level of histochemically reactive zinc (principally synaptic zinc) was significantly reduced in the apoE-deficient brain compared to wild-type. This reduction was accompanied by reduced expressions of the presynaptic zinc transporter, ZnT3, as well as of the δ-subunit of the adaptor protein complex-3 (AP3δ), which is responsible for post-translational stability and activity of ZnT3. In addition, the level of histochemically reactive zinc was also decreased in the cerebrovascular micro-vessels of apoE-deficient mice, the site of cerebral amyloid angiopathy in AD. These results suggest that apoE may affect the cerebral free zinc pool that contributes to AD pathology.

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Acknowledgements

This study was supported by funds from the Korea Healthcare Technology R&D Project, Ministry for Health and Welfare, Republic of Korea (A080201 to JYL), from Asan Institute for Life Sciences (2008-396 to JYL), from the Korea Research Foundation (NRL2009-0066335 and KPSEP2009-0081487 to JYK), and from the National Health and Medical Research Council of Australia, Australian Research Council and the Alzheimer’s Association (to AIB).

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Correspondence to Ashley I. Bush or Jae-Young Koh.

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Lee, JY., Cho, E., Kim, TY. et al. Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain. Biometals 23, 1085–1095 (2010). https://doi.org/10.1007/s10534-010-9354-9

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  • DOI: https://doi.org/10.1007/s10534-010-9354-9

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