No abstract

TREM2 is exclusively expressed by microglia in the brain and is strongly linked to the risk for Alzheimer’s disease (AD). As microglial responses modulated by TREM2 are central to AD pathogenesis, enhancing TREM2 signaling has been explored as an AD therapeutic strategy. However, the effective therapeutic window targeting TREM2 is unclear. Here, by using microglia-specific inducible mouse models overexpressing human wild-type TREM2 (TREM2-WT) or R47H risk variant (TREM2-R47H), we show that TREM2-WT expression reduces amyloid deposition and neuritic dystrophy only during the early amyloid seeding stage, whereas TREM2-R47H exacerbates amyloid burden during the middle amyloid rapid growth stage. Single-cell RNA sequencing reveals suppressed disease-associated microglia (DAM) signature and reduced DAM population upon TREM2-WT expression in the early stage, whereas upregulated antigen presentation pathway is detected with TREM2-R47H expression in the middle stage. Together, our findings highlight the dynamic effects of TREM2 in modulating AD pathogenesis and emphasize the beneficial effect of enhancing TREM2 function in the early stage of AD development.

No abstract

Summary. Results obtained in the sheep cell‐rosette test for identification of human T lymphocytes are strongly dependant on the origin of the sheep erythrocytes. Other factors which influence rosette formation are the duration of incubation of the lymphocyte erythrocyte mixture and the concentration of serum used. The most reproducible results, giving a range of 55–75% RFC among the peripheral blood lymphocytes of healthy adults, are obtained by leaving the cell mixture overnight at room temperature in the presence of 10–25% serum.The spontaneous sheepcell rosette test appears to be a useful means of identifying human T lymphocytes (Jondal et al, 1972; Papamichail et al, 1972; Wortis et al, 1973; Yata et al, 1973); there are, however, striking discrepancies in the percentage of rosette‐forming cells (RFC) reported among the peripheral blood lymphocytes of healthy donors for the figures quoted range from under 5% (Bach et al, 1969) to almost 80% (Bentwich et al, 1973). There are many points of variation between the techniques employed (Bach et al, 1969; Coombs et al. 1970; Brain et al, 1970; Lay et al, 1971; Jondal et al, 1972; Papamichail et al, 1972; Wybran et al, 1973; Yata et al, 1973; Bentwich et al, 1973) but the importance of such technical variations is largely unknown (Urbaniak et al, 1973). In the present study, several of the points of variance between published techniques have been analysed.