| First Author | Amano A | Year | 2023 |
| Journal | J Nanobiotechnology | Volume | 21 |
| Issue | 1 | Pages | 36 |
| PubMed ID | 36721182 | Mgi Jnum | J:348788 |
| Mgi Id | MGI:7643650 | Doi | 10.1186/s12951-023-01772-y |
| Citation | Amano A, et al. (2023) Peripheral administration of nanomicelle-encapsulated anti-Abeta oligomer fragment antibody reduces various toxic Abeta species in the brain. J Nanobiotechnology 21(1):36 |
| abstractText | BACKGROUND: Although a large amount of evidence has revealed that amyloid beta (Abeta), especially Abeta oligomers, protofibrils, and pyroglutamated Abetas, participate primarily in the pathophysiological processes of Alzheimer's disease, most clinical trials of anti-Abeta antibody therapy have never acquired successful efficacy in human clinical trials, partly because peripheral administration of antibody medications was unable to deliver sufficient amounts of the molecules to the brain. Recently, we developed polymeric nanomicelles capable of passing through the blood-brain barrier that function as chaperones to deliver larger amounts of heavy molecules to the brain. Herein, we aimed to evaluate the efficacy of newly developed antibody 6H4 fragments specific to Abeta oligomers encapsulated in polymeric nanomicelles on the development of Alzheimer's disease pathology in Alzheimer's disease model mice at the age of emergence of early Alzheimer's disease pathology. RESULTS: During the 10-week administration of 6H4 antibody fragments in polymeric nanomicelles, a significant reduction in the amounts of various toxic Abeta species, such as Abeta oligomers, toxic Abeta conformers, and pyroglutamated Abetas in the brain was observed. In addition, immunohistochemistry indicated inhibition of diameters of Abeta plaques, Abeta-antibody immunoreactive areas, and also plaque core formation. Behavioral analysis of the mice model revealed that the 6H4 fragments-polymeric nanomicelle group was significantly better at maintaining long-term spatial reference memory in the probe and platform tests of the water maze, thereby indicating inhibition of the pathophysiological process of Alzheimer's disease. CONCLUSIONS: The results indicated that the strategy of reducing toxic Abeta species in early dementia owing to Alzheimer's disease by providing sufficient antibodies in the brain may modify Alzheimer's disease progression. |
