Authors retract study suggesting magnesium prevents Alzheimer’s in mice

The authors of a 2013 Journal of Neuroscience study suggesting that “elevation of brain magnesium…may have therapeutic potential for treating [Alzheimer’s disease] in humans” have retracted it after finding errors in the work.

Here’s the original abstract:

Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer’s disease (AD) and might underlie memory impairment. Our previous work demonstrated that the magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we investigated whether elevation of brain magnesium by the use of a recently developed compound, magnesium-l-threonate (MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic (Tg) mouse model of AD. MgT treatment reduced Aβ plaque and prevented synapse loss and memory decline in the Tg mice. Strikingly, MgT treatment was effective even when given to the mice at the end stage of their AD-like pathological progression. To explore how elevation of brain magnesium ameliorates the AD-like pathologies in the brains of Tg mice, we studied molecules critical for APP metabolism and signaling pathways implicated in synaptic plasticity/density. In the Tg mice, the NMDAR/CREB/BDNF signaling was downregulated, whereas calpain/calcineurin/Cdk5 neurodegenerative signaling and β-secretase (BACE1) expression were upregulated. MgT treatment prevented the impairment of these signaling pathways, stabilized BACE1 expression, and reduced soluble APPβ and β-C-terminal fragments in the Tg mice. At the molecular level, elevation of extracellular magnesium prevented the high-Aβ-induced reductions in synaptic NMDARs by preventing calcineurin overactivation in hippocampal slices. Correlation studies suggested that the protection of NMDAR signaling might underlie the stabilization of BACE1 expression. Our results suggest that elevation of brain magnesium exerts substantial synaptoprotective effects in a mouse model of AD and may have therapeutic potential for treating AD in humans.

According to the notice:

At the request of the authors, The Journal of Neuroscience is retracting “Elevation of Brain Magnesium Prevents and Reverses Cognitive Deficits and Synaptic Loss in Alzheimer’s Disease Mouse Model” by Wei Li, Jia Yu, Yong Liu, Xiaojie Huang, Nashat Abumaria, Ying Zhu, Xian Huang, Wenxiang Xiong, Chi Ren, Xian-Guo Liu, Dehua Chui, and Guosong Liu, which appeared on pages 8423–8441 of the May 8, 2013 issue. The authors report, “This article described the effects of elevating brain magnesium on preventing and reversing cognitive deficits in an Alzheimer’s disease mouse model. During recent efforts to extend this work, we discovered errors in the quantification of the expression and/or phosphorylation of a subset of signaling pathways, particularly related to Figures 4 and 5D. Despite these errors, the major conclusions of the paper remain substantiated. As any correction will require substantial rewriting of the manuscript, we ask to withdraw the article. A corrected treatment will be published in the future. We apologize for any confusion caused by this error.”

The study has been cited twice, according to Thomson Scientific’s Web of Knowledge.

Hat tip: Rolf Degen

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