| First Author | Wittnam JL | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 11 | Pages | 8154-62 |
| PubMed ID | 22267726 | Mgi Jnum | J:182761 |
| Mgi Id | MGI:5316551 | Doi | 10.1074/jbc.M111.308601 |
| Citation | Wittnam JL, et al. (2012) Pyroglutamate amyloid beta (Abeta) aggravates behavioral deficits in transgenic amyloid mouse model for Alzheimer disease. J Biol Chem 287(11):8154-62 |
| abstractText | Pyroglutamate-modified Abeta peptides at amino acid position three (Abeta(pE3-42)) are gaining considerable attention as potential key players in the pathogenesis of Alzheimer disease (AD). Abeta(pE3-42) is abundant in AD brain and has a high aggregation propensity, stability and cellular toxicity. The aim of the present work was to study the direct effect of elevated Abeta(pE3-42) levels on ongoing AD pathology using transgenic mouse models. To this end, we generated a novel mouse model (TBA42) that produces Abeta(pE3-42). TBA42 mice showed age-dependent behavioral deficits and Abeta(pE3-42) accumulation. The Abeta profile of an established AD mouse model, 5XFAD, was characterized using immunoprecipitation followed by mass spectrometry. Brains from 5XFAD mice demonstrated a heterogeneous mixture of full-length, N-terminal truncated, and modified Abeta peptides: Abeta(1-42), Abeta(1-40), Abeta(pE3-40), Abeta(pE3-42), Abeta(3-42), Abeta(4-42), and Abeta(5-42). 5XFAD and TBA42 mice were then crossed to generate transgenic FAD42 mice. At 6 months of age, FAD42 mice showed an aggravated behavioral phenotype compared with single transgenic 5XFAD or TBA42 mice. ELISA and plaque load measurements revealed that Abeta(pE3) levels were elevated in FAD42 mice. No change in Abeta(x)(-42) or other Abeta isoforms was discovered by ELISA and mass spectrometry. These observations argue for a seeding effect of Abeta(pE-42) in FAD42 mice. |
