| First Author | Saito T | Year | 2011 |
| Journal | Nat Neurosci | Volume | 14 |
| Issue | 8 | Pages | 1023-32 |
| PubMed ID | 21725313 | Mgi Jnum | J:175901 |
| Mgi Id | MGI:5287914 | Doi | 10.1038/nn.2858 |
| Citation | Saito T, et al. (2011) Potent amyloidogenicity and pathogenicity of Abeta43. Nat Neurosci 14(8):1023-32 |
| abstractText | The amyloid-beta peptide Abeta42 is known to be a primary amyloidogenic and pathogenic agent in Alzheimer's disease. However, the role of Abeta43, which is found just as frequently in the brains of affected individuals, remains unresolved. We generated knock-in mice containing a pathogenic presenilin-1 R278I mutation that causes overproduction of Abeta43. Homozygosity was embryonic lethal, indicating that the mutation involves a loss of function. Crossing amyloid precursor protein transgenic mice with heterozygous mutant mice resulted in elevated Abeta43, impairment of short-term memory and acceleration of amyloid-beta pathology, which accompanied pronounced accumulation of Abeta43 in plaque cores similar in biochemical composition to those observed in the brains of affected individuals. Consistently, Abeta43 showed a higher propensity to aggregate and was more neurotoxic than Abeta42. Other pathogenic presenilin mutations also caused overproduction of Abeta43 in a manner correlating with Abeta42 and with the age of disease onset. These findings indicate that Abeta43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo. |
