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N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models

Savastano A, Klafki H, Haussman U, Oberstein T, Muller P, Wirths O, Wiltfang J, Bayer TA (2016)

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Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 49

Pages Range: 101-10

Journal Issue: 1

DOI: 10.3233/JAD-150394

Abstract

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

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How to cite

APA:

Savastano, A., Klafki, H., Haussman, U., Oberstein, T., Muller, P., Wirths, O.,... Bayer, T.A. (2016). N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models. Journal of Alzheimer's Disease, 49(1), 101-10. https://dx.doi.org/10.3233/JAD-150394

MLA:

Savastano, Adriana, et al. "N-truncated Aβ2-X starting with position two in sporadic Alzheimer's disease cases and two Alzheimer mouse models." Journal of Alzheimer's Disease 49.1 (2016): 101-10.

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