{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:27:41Z","timestamp":1777393661592,"version":"3.51.4"},"reference-count":23,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2015,11,3]]},"abstract":"<jats:p>According to the modified amyloid hypothesis, the key event in the pathogenesis of Alzheimer\u2019s disease (AD) is the deposition of neurotoxic amyloid \u03b2-peptides (A\u03b2s) in plaques and cerebral blood vessels. Additionally to full-length peptides, a great diversity of N-truncated A\u03b2 variants is derived from the larger amyloid-\u03b2 protein precursor (A\u03b2PP). Vast evidence suggests that A\u03b2x-42 isoforms play an important role in triggering neurodegeneration due to their high abundance, amyloidogenic propensity and toxicity. Although N-truncated A\u03b2 peptides and A\u03b2x-42 species appear to be the crucial players in AD etiology, the A\u03b22-X isoforms did not receive much attention yet. The present study is the first to show immunohistochemical evidence of A\u03b22-X in cases of AD and its distribution in A\u03b2PP\/PS1KI and 5XFAD transgenic mouse models using a novel antibody pAB77 that has been developed using A\u03b22-14 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\u03b2 deposits and minor CAA staining. Western blotting and a capillary isoelectric focusing immunoassay demonstrated the high specificity of the antibody pAb77 against A\u03b2-variants starting with the N-terminal Alanine-2.<\/jats:p>","DOI":"10.3233\/jad-150394","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T11:24:35Z","timestamp":1446549875000},"page":"101-110","source":"Crossref","is-referenced-by-count":17,"title":["N-Truncated A\u03b22-X Starting with Position Two in Sporadic Alzheimer\u2019s Disease Cases and Two Alzheimer Mouse Models"],"prefix":"10.1177","volume":"49","author":[{"given":"Adriana","family":"Savastano","sequence":"first","affiliation":[{"name":"Georg-August-University G\u00f6ttingen, University Medicine G\u00f6ttingen, Department of Psychiatry and Psychotherapy, G\u00f6ttingen, Germany"}]},{"given":"Hans","family":"Klafki","sequence":"additional","affiliation":[{"name":"Georg-August-University G\u00f6ttingen, University Medicine G\u00f6ttingen, Department of Psychiatry and Psychotherapy, G\u00f6ttingen, Germany"},{"name":"LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany"}]},{"given":"Ute","family":"Hau\u00dfmann","sequence":"additional","affiliation":[{"name":"LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany"}]},{"given":"Timo Jan","family":"Oberstein","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany"}]},{"given":"Petr","family":"Muller","sequence":"additional","affiliation":[{"name":"Moravian Biotechnology, Brno, Czech Republic"}]},{"given":"Oliver","family":"Wirths","sequence":"additional","affiliation":[{"name":"Georg-August-University G\u00f6ttingen, University Medicine G\u00f6ttingen, Department of Psychiatry and Psychotherapy, G\u00f6ttingen, Germany"}]},{"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[{"name":"Georg-August-University G\u00f6ttingen, University Medicine G\u00f6ttingen, Department of Psychiatry and Psychotherapy, G\u00f6ttingen, Germany"}]},{"given":"Thomas A.","family":"Bayer","sequence":"additional","affiliation":[{"name":"Georg-August-University G\u00f6ttingen, University Medicine G\u00f6ttingen, Department of Psychiatry and Psychotherapy, G\u00f6ttingen, Germany"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-150394_ref1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"10.3233\/JAD-150394_ref2","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"10.3233\/JAD-150394_ref3","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic Abeta oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"29","author":"Benilova","year":"2012","journal-title":"Nat Neurosci"},{"key":"10.3233\/JAD-150394_ref4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1750-3639.2001.tb00376.x","article-title":"Key factors in Alzheimer\u2019s disease: Beta-amyloid precursor protein processing, metabolism and intraneuronal transport","volume":"11","author":"Bayer","year":"2001","journal-title":"Brain Pathol"},{"key":"10.3233\/JAD-150394_ref5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s00401-014-1287-x","article-title":"Focusing the amyloid cascade hypothesis on N-truncated Abeta peptides as drug targets against Alzheimer\u2019s disease","volume":"127","author":"Bayer","year":"2014","journal-title":"Acta Neuropathol"},{"issue":"Pt A","key":"10.3233\/JAD-150394_ref6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mcn.2015.02.016","article-title":"Current and future implications of basic and translational research on amyloid-\u03b2 peptide production and removal pathways","volume":"66","author":"Bohm","year":"2015","journal-title":"Mol Cell Neurosci"},{"key":"10.3233\/JAD-150394_ref7","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Down syndrome","volume":"82","author":"Masters","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-150394_ref8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/jms.739","article-title":"Quantification of the Abeta peptide in Alzheimer\u2019s plaques by laser dissection microscopy combined with mass spectrometry","volume":"40","author":"Rufenacht","year":"2005","journal-title":"J Mass Spectrom"},{"key":"10.3233\/JAD-150394_ref9","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.neuroscience.2006.08.027","article-title":"High sensitivity analysis of amyloid-beta peptide composition in amyloid deposits from human and PS2APP mouse brain","volume":"143","author":"G\u00fcntert","year":"2006","journal-title":"Neuroscience"},{"key":"10.3233\/JAD-150394_ref10","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00401-010-0690-1","article-title":"Mass spectrometric characterization of brain amyloid beta isoform signatures in familial and sporadic Alzheimer\u2019s disease","volume":"120","author":"Portelius","year":"2010","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-150394_ref11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1365-2990.2006.00696.x","article-title":"Quantification of Alzheimer pathology in ageing and dementia: Age-related accumulation of amyloid-\u03b2 (42) peptide in vascular dementia","volume":"32","author":"Lewis","year":"2006","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.3233\/JAD-150394_ref12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.nbd.2014.08.031","article-title":"Astrocytes and microglia but not neurons preferentially generate N-terminally truncated Abeta peptides","volume":"73","author":"Oberstein","year":"2015","journal-title":"Neurobiol Dis"},{"key":"10.3233\/JAD-150394_ref13","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/S0002-9440(10)63388-3","article-title":"Massive CA1\/2 neuronal loss with intraneuronal and N-terminal truncated Abeta 42 accumulation in a novel Alzheimer transgenic model","volume":"165","author":"Casas","year":"2004","journal-title":"Am J Pathol"},{"key":"10.3233\/JAD-150394_ref14","doi-asserted-by":"crossref","first-page":"8142","DOI":"10.1021\/ac401055y","article-title":"Analysis of amino-terminal variants of amyloid-beta peptides by capillary isoelectric focusing immunoassay","volume":"85","author":"Haussmann","year":"2013","journal-title":"Anal Chem"},{"key":"10.3233\/JAD-150394_ref15","doi-asserted-by":"crossref","first-page":"42645","DOI":"10.1074\/jbc.M102790200","article-title":"Elevation of beta-amyloid peptide 2-42 in sporadic and familial Alzheimer\u2019s disease and its generation in PS1 knockout cells","volume":"276","author":"Wiltfang","year":"2001","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-150394_ref16","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.3233\/JAD-142463","article-title":"Neprilysin deficiency alters the neuropathological and behavioral phenotype in the 5XFAD mouse model of Alzheimer\u2019s disease","volume":"44","author":"Huttenrauch","year":"2015","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-150394_ref17","doi-asserted-by":"crossref","first-page":"196.e129","DOI":"10.1016\/j.neurobiolaging.2010.05.027","article-title":"Motor deficits, neuron loss, and reduced anxiety coinciding with axonal degeneration and intraneuronal Abeta aggregation in the 5XFAD mouse model of Alzheimer\u2019s disease","volume":"33","author":"Jawhar","year":"2012","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-150394_ref18","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00401-013-1129-2","article-title":"N-truncated amyloid beta (Abeta) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits","volume":"126","author":"Bouter","year":"2013","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-150394_ref19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1006\/abbi.1993.1112","article-title":"Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer\u2019s disease","volume":"301","author":"Miller","year":"1993","journal-title":"Arch Biochem Biophys"},{"key":"10.3233\/JAD-150394_ref20","doi-asserted-by":"crossref","first-page":"33747","DOI":"10.1074\/jbc.M111.246561","article-title":"Beta-amyloid peptide variants in brains and cerebrospinal fluid from amyloid precursor protein (APP) transgenic mice: Comparison with human Alzheimer amyloid","volume":"286","author":"Schieb","year":"2011","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-150394_ref21","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00401-009-0539-7","article-title":"APP\/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy","volume":"117","author":"Breyhan","year":"2009","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-150394_ref22","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: Potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-150394_ref23","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological staging of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-150394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:01:20Z","timestamp":1777370480000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-150394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,3]]},"references-count":23,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jad-150394","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,3]]}}}