Citations

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.

Four corner arthrodesis and proximal row carpectomy are the most common techniques for the management of advanced radiocarpal arthritis due to longstanding scapholunate instability and scaphoid nonunion. The advantages and short comings of each technique have been well defined in the literature. Advancements in joint replacement and arthroscopic surgery have resulted in new operations to manage radiocarpal and midcarpal arthritis. Most of these new procedures are modifications of the two classical operations, but some use modern implants and newer materials. New individualized options, like osteochondral grafting in combination with proximal row carpectomy or (arthroscopic) distal resection of the scaphoid, allowed us to improve our treatment and offer patients less invasive but equally effective procedures. We consider that four corner arthrodesis and proximal row carpectomy should not always be standard management for advanced radiocarpal arthritis.