{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:35:03Z","timestamp":1791081303131,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P01 AG003991"],"award-info":[{"award-number":["P01 AG003991"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cerebral amyloid angiopathy (CAA) shares amyloid\u2010\u03b2 (A\u03b2) deposition as a pathological hallmark with the extracellular plaques of Alzheimer's disease (AD). While both disease processes involve progressive, decades\u2010long deposition of fibrillar A\u03b2 peptide, they differ in isoform composition. We hypothesized that post\u2010translational modifications (PTMs) on A\u03b2 would also differ between CAA and parenchymal plaques. Using Lys\u2010N enzymatic digestion followed by quantitative mass spectrometry, we profiled A\u03b2 isoforms and N\u2010terminus PTMs (aspartic acid isomerization and pyroglutamate formation) across CAA severity and compared them to parenchymal plaque A\u03b2 in AD. Moderate to severe CAA were dominated by intact N\u2010terminus (A\u03b2\n                    <jats:sub>1\u2010x<\/jats:sub>\n                    \u2009~\u200995%) with minimal N\u2010truncated species (A\u03b2\n                    <jats:sub>2\u2010x<\/jats:sub>\n                    , A\u03b2\n                    <jats:sub>3pGlu\u2010x<\/jats:sub>\n                    , and A\u03b2\n                    <jats:sub>4\u2010x<\/jats:sub>\n                    ), whereas parenchymal plaques displayed diverse N\u2010terminus truncations and PTMs. Increasing CAA severity correlated with a shift from longer, hydrophobic C\u2010terminal isoforms (A\u03b2\n                    <jats:sub>41<\/jats:sub>\n                    , A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    , and A\u03b2\n                    <jats:sub>43<\/jats:sub>\n                    ) to shorter, less hydrophobic C\u2010terminal isoforms (A\u03b2\n                    <jats:sub>37<\/jats:sub>\n                    , A\u03b2\n                    <jats:sub>38<\/jats:sub>\n                    , A\u03b2\n                    <jats:sub>39<\/jats:sub>\n                    , and A\u03b2\n                    <jats:sub>40<\/jats:sub>\n                    ). Importantly, moderate and severe CAA displayed minimal isomerization of Asp1 and Asp7 residues. These patterns suggest distinct A\u03b2 aggregation mechanisms in CAA versus parenchymal plaques. We propose that the intact and unmodified N\u2010terminus found in CAA is due to its inclusion within the protofibril structure making them less disordered and inaccessible to post\u2010translational modifications, in contrast to plaque\u2010associated A\u03b2. These biochemical differences may reflect underlying structural distinctions in protofibril architectures, with potential implications for biomarker development for early CAA detection and therapeutic targeting of vascular versus parenchymal A\u03b2.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70335-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70335","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T07:39:15Z","timestamp":1766993955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Post\u2010Translational Modifications Distinguish Amyloid\u2010\u03b2 Isoforms in Cerebral Amyloid Angiopathy and Alzheimer's Disease"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-6733","authenticated-orcid":false,"given":"Srinivas","family":"Koutarapu","sequence":"first","affiliation":[{"name":"Department of Pathology &amp; Immunology, Division of Neuropathology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaleigh F.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology, Division of Neuropathology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid A.","family":"Coyle","sequence":"additional","affiliation":[{"name":"Tracy Family SILQ Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jogender","family":"Mehla","sequence":"additional","affiliation":[{"name":"Taylor Family Department of Neurosurgery Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Tracy Family SILQ Center Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri 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