| First Author | Savastano A | Year | 2016 |
| Journal | J Alzheimers Dis | Volume | 49 |
| Issue | 1 | Pages | 101-10 |
| PubMed ID | 26529393 | Mgi Jnum | J:286210 |
| Mgi Id | MGI:6402334 | Doi | 10.3233/JAD-150394 |
| Citation | Savastano A, et al. (2016) N-truncated Abeta2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models. J Alzheimers Dis 49(1):101-10 |
| abstractText | According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid beta-peptides (Abetas) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated Abeta variants is derived from the larger amyloid-beta protein precursor (AbetaPP). Vast evidence suggests that Abetax-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Abeta peptides and Abetax-42 species appear to be the crucial players in AD etiology, the Abeta2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of Abeta2-X in cases of AD and its distribution in AbetaPP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using Abeta2-14 as antigen. Positive plaques and congophilic amyloid angiopathy (CAA) were observed in AD cases and in both mouse models. While in AD cases, abundant CAA and less pronounced plaque pathology was evident, the two mouse models showed predominantly extracellular Abeta deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against Abeta-variants starting with the N-terminal Alanine-2. |
