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Acknowledgements

This work was partly supported by grants from the Japan Society for the Promotion of Science (Grant Numbers

22221004, 17H01391 to Y.N.), the Ministry of Health, Labour, and Welfare, Japan (Grant Number H20-ninchisho-ippan-004 to Y.N.), and the Uehara Memorial Foundation to Y. N. We thank Edanz Group (www.edanz​

editi​ng.com/ac) for editing a draft of this manuscript. We thank E. Koba, R. Ugawa and K. Ichikawa (Laboratory

for Technical Support, Medical Institute of Bioregulation, Kyushu University) for performing the microarray

analysis, transmission electron microscope and preparation of paraffin-embedded blocks. We also thank S.

Kitamura, K. Nakabeppu, T. Kuwano, and T. Koizumi for their technical assistance.

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Author contributions

S.O. carried out behavioral analysis and immunostaining, microarray data analysis, statistical analysis of data

and wrote the first draft and revised manuscript. J.L. performed experiments, K.S. performed Western blotting

and prepared sample for electron microscopy and instructed all animal experiments, Z.S. and D. T. instructed

all animal experiments, N.A prepared sample for Western blotting. F.M.L. provided 3xTg-AD mice and Y.N.

conceived the project, analyzed the data, and edited the manuscript. All authors commented on the manuscript.

Competing interests The authors declare no competing interests.

Additional information

Supplementary Information The online version contains supplementary material available at https​://doi.

org/10.1038/s4159​8-021-84640​-9.

Correspondence and requests for materials should be addressed to Y.N.

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