DAM microglia upregulate TREM2 as a response to pathological protein aggregates, but whether sustaining or dampening this phenotype is beneficial remains contested. Early TREM2 activation appears protective, but chronic overactivation may drive neuroinflammatory damage. Resolving this timing-dependent duality is critical for anti-AD drug development.
The disease-associated microglia (DAM) phenotype involves TREM2 upregulation, but whether therapeutic agonism or antagonism of TREM2 is beneficial remains contested across disease stages.