Further, Trem2 KO or TREM2 R47H promote pathological tau seeding in an APP/PS1 AD mouse model [42]; Trem2 deletion also aggravated tau spreading/pathology in a P301L tau/PS2 APP mouse model [41] as well as in 5xFAD brain injected with tau aggregates from human AD brain [21], together suggesting that in addition to Aβ [69], TREM2 dysfunction can also promote tau pathology. This evidence concerns the gene APP and Alzheimer disease.