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In addition to \u2018full\u2010length\u2019 A\u03b2 starting with aspartic acid (Asp\u20101), considerable amounts of various shorter, N\u2010terminally truncated A\u03b2 peptides have been identified by mass spectrometry in autopsy samples from individuals with AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Selectivity of several antibodies detecting full\u2010length, total or N\u2010terminally truncated A\u03b2 species has been characterized with capillary isoelectric focusing assays using a set of synthetic A\u03b2 peptides comprising different N\u2010termini. We further assessed the N\u2010terminal heterogeneity of extracellular and vascular A\u03b2 peptide deposits in the human brain by performing immunohistochemical analyses using sporadic AD cases with antibodies targeting different N\u2010terminal residues, including the biosimilar antibodies Bapineuzumab and Crenezumab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While antibodies selectively recognizing A\u03b2<jats:sub>1\u2013<\/jats:sub><jats:italic><jats:sub>x<\/jats:sub><\/jats:italic> showed a much weaker staining of extracellular plaques and tended to accentuate cerebrovascular amyloid deposits, antibodies detecting A\u03b2 starting with phenylalanine at position 4 of the A\u03b2 sequence showed abundant amyloid plaque immunoreactivity in the brain parenchyma. The biosimilar antibody Bapineuzumab recognized A\u03b2 starting at Asp\u20101 and demonstrated abundant immunoreactivity in AD brains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In contrast to other studied A\u03b2<jats:sub>1\u2013<\/jats:sub><jats:italic><jats:sub>x<\/jats:sub><\/jats:italic>\u2010specific antibodies, Bapineuzumab displayed stronger immunoreactivity on fixed tissue samples than with sodium dodecyl sulfate\u2010denatured samples on Western blots. This suggests conformational preferences of this antibody. The diverse composition of plaques and vascular deposits stresses the importance of understanding the roles of various A\u03b2 variants during disease development and progression in order to generate appropriate target\u2010developed therapies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12637","type":"journal-article","created":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T20:30:00Z","timestamp":1591302600000},"page":"673-685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["N\u2010terminal heterogeneity of parenchymal and vascular amyloid\u2010\u03b2 deposits in Alzheimer\u2019s disease"],"prefix":"10.1111","volume":"46","author":[{"given":"S.","family":"Zampar","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center (UMG) Georg\u2010August\u2010University G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. W.","family":"Klafki","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center (UMG) Georg\u2010August\u2010University G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Sritharen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center (UMG) Georg\u2010August\u2010University G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. A.","family":"Bayer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center (UMG) Georg\u2010August\u2010University G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wiltfang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Medical Center (UMG) Georg\u2010August\u2010University G\u00f6ttingen Germany"},{"name":"Neurosciences and Signaling Group Department of Medical Sciences Institute of Biomedicine (iBiMED) University of Aveiro Aveiro Portugal"},{"name":"German Center for Neurodegenerative Diseases (DZNE) G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rostagno","sequence":"additional","affiliation":[{"name":"Departments of Pathology New York University School of Medicine New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Ghiso","sequence":"additional","affiliation":[{"name":"Departments of Pathology New York University School of Medicine New York NY USA"},{"name":"Department of Psychiatry New York University School of Medicine New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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