The APP/PS1 (APPswe/PSEN1dE9) double-transgenic mice (40) were obtained from the Model Animal Research Center of Nanjing University (Nanjing, China). The 5XFAD mice overexpressing the K670 N/M671 L (Swedish), I716V (Florida), and V717I (London) mutations in human APP (695), as well as M146 L and L286 V mutations in human PS1 (41), were provided by C. Zhang (Peking University, Beijing, China). Trem2 conventional KO mice were generated by deleting 7 base pairs (AAGCGGA) of exon2 from 384 to 390 via the CRISPR-Cas9 system. Genotypes were confirmed by PCR analysis of tail biopsy specimens. Mice of mixed genotypes were housed four to five per cage with a 12-hour light/12-hour dark cycle and food and water ad libitum. Male mice (C56BL/6J background) were used within all experiments to avoid the influence of gender. All experimental animal procedures were approved by the Institutional Animal Care and Use Committees of the Beijing Institute of Basic Medical Sciences.

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