Abstract
Trem2 deficiency is protective early but detrimental late in disease progression in an amyloid mouse model of Alzheimer's disease
Neurobiology of aging, Vol.39(Suppl 1), pp.S17-S17
03/2016
DOI: 10.1016/j.neurobiolaging.2016.01.082
Abstract
Variants in the triggering receptor expressed on myeloid cells 2 (Trem2) gene confer high risk for developing Alzheimer's disease (AD), and thus Trem2 has been proposed to be a promising new therapeutic target for AD drug development. Trem2 an important modulator of myeloid cell phenotypes, but its function in the context of AD is contentious. We have recently shown that Trem2 deficiency reduces myeloid cell activation and ameliorates AD-like pathologies in 4-month-old APPPS1-21 mice. However, others have shown that Trem2 deficiency instead increases amyloid pathology in 8-month old 5XFAD mice. One possible explanation for these divergent findings is that Trem2 has differential roles early and late in disease progression. Here, we assessed the effects of Trem2 deficiency on myeloid cell function and amyloid deposition in 2-month-old and 8-month-old APPPS1-21;Trem2-/- mice compared to APPPS1-21;Trem2+/+ controls. Trem2 deficiency reduced proliferation of brain myeloid cells and affected cell survival, phagocytosis and accumulation around plaques at every timepoint examined. Furthermore, we found that Trem2 deficiency reduced pathology in brain regions in early stages of plaque accumulation, but worsened pathology at later stages in amyloid deposition. These findings support a disease progression-dependent role for Trem2 on AD pathology, suggesting that Trem2 itself might be detrimental early in the development of amyloid pathology, but be protective later in the disease process. These studies provide important insights for the development of Trem2-directed therapeutics, suggesting that different Trem2 targeting strategies might be required at different stages of AD progression.
Details
- Title: Subtitle
- Trem2 deficiency is protective early but detrimental late in disease progression in an amyloid mouse model of Alzheimer's disease
- Creators
- Taylor Jay - Case Western Reserve UniversityAnna Hirsch - Anna Needs Neuroblastoma AnswersMargaret Broihier - Anna Needs Neuroblastoma AnswersGary Landreth - Anna Needs Neuroblastoma Answers
- Resource Type
- Abstract
- Publication Details
- Neurobiology of aging, Vol.39(Suppl 1), pp.S17-S17
- DOI
- 10.1016/j.neurobiolaging.2016.01.082
- ISSN
- 0197-4580
- eISSN
- 1558-1497
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9985113263102771
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