ORCID: https://orcid.org/0000-0002-4869-1627 and Butovsky, Oleg
(2017):
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
In: Immunity, Vol. 47, No. 3: pp. 566-581
Abstract
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic b-amyloid (Ab)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons. TREM2 (triggering receptor expressed on myeloid cells 2) induced APOE signaling, and targeting the TREM2-APOE pathway restored the homeostatic signature of microglia in ALS and AD mouse models and prevented neuronal loss in an acute model of neurodegeneration. APOE-mediated neurodegenerative microglia had lost their tolerogenic function. Our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target that could aid in the restoration of homeostatic microglia.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine |
| Subjects: | 600 Technology > 610 Medicine and health |
| ISSN: | 1074-7613 |
| Language: | English |
| Item ID: | 52150 |
| Date Deposited: | 14. Jun 2018, 09:49 |
| Last Modified: | 04. Nov 2020, 13:30 |
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