| First Author | Mitsubori M | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 549 |
| Pages | 67-74 | PubMed ID | 33667711 |
| Mgi Jnum | J:305937 | Mgi Id | MGI:6705938 |
| Doi | 10.1016/j.bbrc.2021.02.081 | Citation | Mitsubori M, et al. (2021) Identification of highest neurotoxic amyloid-beta plaque type showing reduced contact with astrocytes. Biochem Biophys Res Commun 549:67-74 |
| abstractText | Amyloid-beta (Abeta) plaques are strongly associated with the development of Alzheimer's disease (AD). However, it remains unclear how morphological differences in Abeta plaques determine the pathogenesis of Abeta. Here, we categorized Abeta plaques into four types based on the macroscopic features of the dense core, and found that the Abeta-plaque subtype containing a larger dense core showed the strongest association with neuritic dystrophy. Astrocytes dominantly accumulated toward these expanded/dense-core-containing Abeta plaques. Previously, we indicated that deletion of the mitochondrial ubiquitin ligase MITOL/MARCH5 triggers mitochondrial impairments and exacerbates cognitive decline in a mouse model with AD-related Abeta pathology. In this study, MITOL deficiency accelerated the formation of expanded/dense-core-containing Abeta plaques, which showed reduced contacts with astrocytes, but not microglia. Our findings suggest that expanded/dense-core-containing Abeta-plaque formation enhanced by the alteration of mitochondrial function robustly contributes to the exacerbation of Abeta neuropathology, at least in part, through the reduced contacts between Abeta plaques and astrocytes. |
