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DAP12 deficiency alters microglia-oligodendrocyte communication and enhances resilience against tau toxicity.
Chen, Hao; Fan, Li; Guo, Qi; Wong, Man Ying; Yu, Fangmin; Foxe, Nessa; Wang, Winston; Nessim, Aviram; Carling, Gillian; Liu, Bangyan; Lopez-Lee, Chloe; Huang, Yige; Amin, Sadaf; Mok, Sue-Ann; Song, Won-Min; Zhang, Bin; Ma, Qin; Fu, Hongjun; Gan, Li; Luo, Wenjie.
Afiliação
  • Chen H; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Fan L; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Guo Q; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH 43210 USA.
  • Wong MY; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Yu F; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Foxe N; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Wang W; Millburn High School, New Jersey, NJ, USA.
  • Nessim A; The State University of New York at Stony Brook, Long Island, New York, USA.
  • Carling G; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Liu B; Program of Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
  • Lopez-Lee C; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Huang Y; Program of Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
  • Amin S; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Mok SA; Program of Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
  • Song WM; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Zhang B; Program of Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
  • Ma Q; Helen and Robert Appel Alzheimer Disease Research Institute, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
  • Fu H; Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB Canada.
  • Gan L; Department of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Luo W; Department of Genetics and Genomic Sciences, Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Res Sq ; 2023 Oct 26.
Article em En | MEDLINE | ID: mdl-37961627
Pathogenic tau accumulation fuels neurodegeneration in Alzheimer's disease (AD). Enhancing aging brain's resilience to tau pathology would lead to novel therapeutic strategies. DAP12 (DNAX-activation protein 12) is critically involved in microglial immune responses. Previous studies have showed that mice lacking DAP12 in tauopathy mice exhibit higher tau pathology but are protected from tau-induced cognitive deficits. However, the exact mechanism remains elusive. Our current study uncovers a novel resilience mechanism via microglial interaction with oligodendrocytes. Despite higher tau inclusions, Dap12 deletion curbs tau-induced brain inflammation and ameliorates myelin and synapse loss. Specifically, removal of Dap12 abolished tau-induced disease-associated clusters in microglia (MG) and intermediate oligodendrocytes (iOli), which are spatially correlated with tau pathology in AD brains. Our study highlights the critical role of interactions between microglia and oligodendrocytes in tau toxicity and DAP12 signaling as a promising target for enhancing resilience in AD.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article