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RETRACTED ARTICLE: Full recovery of the Alzheimer’s disease phenotype by gain of function of vacuolar protein sorting 35

Molecular Psychiatry volume 25, pages 2630–2640 (2020)Cite this article

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This article was retracted on 18 October 2022

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Abstract

Deficit in retromer complex function secondary to lower levels of one of its major components, the vacuolar protein sorting 35 (VPS35), has been reported in Alzheimer’s disease (AD) brains. VPS35 genetic reduction results in increased Aβ levels and synaptic pathology in mouse models of the disease. However, whether restoration of its levels has an effect on the AD-like phenotype which includes Aβ plaques, tau tangles and memory impairments remain unknown. In this paper, we investigated the effect of VPS35 gene delivery into the central nervous system on the development of the neuropathology and behavioral deficits of the triple transgenic (3xTg) mice. Compared with controls, animals overexpressing VPS35 had an amelioration of spatial learning and working memory, which associated with a significant reduction in Aβ levels and deposition and tau phosphorylation. Additionally, the same animals had a significant improvement of synaptic pathology and neuroinflammation. In vitro study confirmed that VPS35 up-regulation by reducing total levels of APP and results in a significant decrease in its metabolic products. Our results demonstrate for the first time that VPS35 is directly involved in the development of AD-like phenotype, and for this reason should be considered as a novel therapeutic target for AD.

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Acknowledgements

Domenico Praticò is the Scott Richards North Star Charitable Foundation Chair for Alzheimer’s Research. This study was supported in part by grants from the National Institute of Health (AG056689, AG055707), and the Scott Richards North Star Charitable Foundation.

Author contribution

J-GL and DP designed the study; J-GL and JC performed the experiments; J-GL and DP analyzed the data and drafted the manuscript. All authors have discussed the results and seen the final version of the paper before submission.

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  1. Alzheimer’s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA

    Jian-Guo Li, Jin Chiu & Domenico Praticò

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  1. Jian-Guo Li
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Correspondence to Domenico Praticò.

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This article has been retracted. Please see the retraction notice for more detail:https://doi.org/10.1038/s41380-022-01814-1

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Li, JG., Chiu, J. & Praticò, D. RETRACTED ARTICLE: Full recovery of the Alzheimer’s disease phenotype by gain of function of vacuolar protein sorting 35. Mol Psychiatry 25, 2630–2640 (2020). https://doi.org/10.1038/s41380-019-0364-x

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