| First Author | Jain N | Year | 2023 |
| Journal | J Exp Med | Volume | 220 |
| Issue | 1 | PubMed ID | 36219197 |
| Mgi Jnum | J:350035 | Mgi Id | MGI:7467280 |
| Doi | 10.1084/jem.20220654 | Citation | Jain N, et al. (2023) Chronic TREM2 activation exacerbates Abeta-associated tau seeding and spreading. J Exp Med 220(1) |
| abstractText | Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-beta (Abeta) plaques, resulting in more diffuse Abeta plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Abeta and tau pathologies in AD. Since genetically decreasing TREM2 function increases Abeta-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading. Using a mouse model of amyloidosis in which AD-tau is injected into the brain to induce Abeta-dependent tau seeding/spreading, we found that chronic administration of an activating TREM2 antibody increases peri-plaque microglial activation but surprisingly increases peri-plaque NP-tau pathology and neuritic dystrophy, without altering Abeta plaque burden. Our data suggest that sustained microglial activation through TREM2 that does not result in strong amyloid removal may exacerbate Abeta-induced tau pathology, which may have important clinical implications. |
