%0 Journal Article %J J Alzheimers Dis %D 2016 %T N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models. %A Savastano, Adriana %A Klafki, Hans %A Haußmann, Ute %A Oberstein, Timo Jan %A Muller, Petr %A Wirths, Oliver %A Wiltfang, Jens %A Bayer, Thomas A %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Animals %K Blotting, Western %K Brain %K Cerebral Amyloid Angiopathy %K Disease Models, Animal %K Female %K Humans %K Male %K Mice %K Mice, Transgenic %K Plaque, Amyloid %X

According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of neurotoxic amyloid β-peptides (Aβs) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated Aβ variants is derived from the larger amyloid-β protein precursor (AβPP). Vast evidence suggests that Aβx-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated Aβ peptides and Aβx-42 species appear to be the crucial players in AD etiology, the Aβ2-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of Aβ2-X in cases of AD and its distribution in AβPP/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using Aβ2-14 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 Aβ deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against Aβ-variants starting with the N-terminal Alanine-2.

%B J Alzheimers Dis %V 49 %P 101-10 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26529393?dopt=Abstract %R 10.3233/JAD-150394