PT  - JOURNAL ARTICLE
AU  - Liu, Jianguo
AU  - Geraghty, Joseph R.
AU  - Schram, Sarah
AU  - Cropper, Haley C.
AU  - Lei, Justin
AU  - Loeb, Jeffrey A.
AU  - Song, Fei
TI  - Prevention of Alzheimer Pathology by Blocking Neuregulin Signaling on Microglia
AID  - 10.1523/ENEURO.0422-23.2023
DP  - 2023 Nov 01
TA  - eneuro
PG  - ENEURO.0422-23.2023
VI  - 10
IP  - 11
4099  - http://www.eneuro.org/content/10/11/ENEURO.0422-23.2023.short
4100  - http://www.eneuro.org/content/10/11/ENEURO.0422-23.2023.full
SO  - eNeuro2023 Nov 01; 10
AB  - Plaque formation, microglial activation, and synaptic loss are pathologic hallmarks of Alzheimer’s disease; however, removing plaques has had little clinical benefit. Here, we show that neuregulin-1, a glial growth factor, induces inflammatory cytokines and promotes phagocytic activity in vitro and augments microglial activation and plaque formation in 5XFAD Alzheimer’s mice. Brain-specific targeting of neuregulin-1 by intraventricular delivery of a novel neuregulin-1 fusion protein antagonist, GlyB4, significantly alters microglial morphology and function to a nonpathogenic morphology in early-stage 5XFAD mice and prevents plaques from forming. Once plaques have already formed, GlyB4 reduces new plaque formation and prevents synaptic loss. Selective, targeted disruption of neuregulin-1 signaling on brain microglia with GlyB4 could be a novel “upstream” approach to slow or stop disease progression in Alzheimer’s disease.