| First Author | Kumar S | Year | 2020 |
| Journal | Acta Neuropathol Commun | Volume | 8 |
| Issue | 1 | Pages | 118 |
| PubMed ID | 32727580 | Mgi Jnum | J:311717 |
| Mgi Id | MGI:6771421 | Doi | 10.1186/s40478-020-00959-w |
| Citation | Kumar S, et al. (2020) Phosphorylated Abeta peptides in human Down syndrome brain and different Alzheimer's-like mouse models. Acta Neuropathol Commun 8(1):118 |
| abstractText | The deposition of neurotoxic amyloid-beta (Abeta) peptides in extracellular plaques in the brain parenchyma is one of the most prominent neuropathological features of Alzheimer's disease (AD), and considered to be closely related to the pathogenesis of this disease. A number of recent studies demonstrate the heterogeneity in the composition of Abeta deposits in AD brains, due to the occurrence of elongated, truncated and post-translationally modified Abeta peptides that have peculiar characteristics in aggregation behavior and biostability. Importantly, the detection of modified Abeta species has been explored to characterize distinct stages of AD, with phosphorylated Abeta being present in the clinical phase of AD. People with Down syndrome (DS) develop AD pathology by 40 years of age likely due to the overproduction of Abeta caused by the additional copy of the gene encoding the amyloid precursor protein on chromosome 21. In the current study, we analysed the deposition of phosphorylated and non-phosphorylated Abeta species in human DS, AD, and control brains. In addition, deposition of these Abeta species was analysed in brains of a series of established transgenic AD mouse models using phosphorylation-state specific Abeta antibodies. Significant amounts of Abeta phosphorylated at serine residue 8 (pSer8Abeta) and unmodified Abeta were detected in the brains of DS and AD cases. The brains of different transgenic mouse models with either only human mutant amyloid precursor protein (APP), or combinations of human mutant APP, Presenilin (PS), and tau transgenes showed distinct age-dependent and spatiotemporal deposition of pSer8Abeta in extracellular plaques and within the vasculature. Together, these results demonstrate the deposition of phosphorylated Abeta species in DS brains, further supporting the similarity of Abeta deposition in AD and DS. Thus, the detection of phosphorylated and other modified Abeta species could contribute to the understanding and dissection of the complexity in the age-related and spatiotemporal deposition of Abeta variants in AD and DS as well as in distinct mouse models. |
