{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:44:37Z","timestamp":1790811877889,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2018\u201002181"],"award-info":[{"award-number":["#2018\u201002181"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["#2019\u201002397"],"award-info":[{"award-number":["#2019\u201002397"]}],"id":[{"id":"10.13039\/501100004359","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":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Familial British dementia (FBD) and familial Danish dementia (FDD) are autosomal dominant forms of dementia caused by mutations in the integral membrane protein 2B (<jats:italic>ITM2B<\/jats:italic>, also known as <jats:italic>BRI2<\/jats:italic>) gene. Secretase processing of mutant BRI2 leads to secretion and deposition of BRI2\u2010derived amyloidogenic peptides, ABri and ADan that resemble APP\/\u03b2\u2010amyloid (A\u03b2) pathology, which is characteristic of Alzheimer's disease (AD). Amyloid pathology in FBD\/FDD manifests itself predominantly in the microvasculature by ABri\/ADan containing cerebral amyloid angiopathy (CAA). While ABri and ADan peptide sequences differ only in a few C\u2010terminal amino acids, CAA in FDD is characterized by co\u2010aggregation of ADan with A\u03b2, while in contrast no A\u03b2 deposition is observed in FBD. The fact that FDD patients display an earlier and more severe disease onset than FBD suggests a potential role of ADan and A\u03b2 co\u2010aggregation that promotes a more rapid disease progression in FDD compared to FBD. It is therefore critical to delineate the chemical signatures of amyloid aggregation in these two vascular dementias. This in turn will increase the knowledge on the pathophysiology of these diseases and the pathogenic role of heterogenous amyloid peptide interactions and deposition, respectively. Herein, we used matrix\u2010assisted laser desorption\/ionization mass spectrometry imaging (MALDI\u2010MSI) in combination with hyperspectral, confocal microscopy based on luminescent conjugated oligothiophene probes (LCO) to delineate the structural traits and associated amyloid peptide patterns of single CAA in postmortem brain tissue of patients with FBD, FDD as well as sporadic CAA without AD (CAA+) that show pronounced CAA without parenchymal plaques. The results show that CAA in both FBD and FDD consist of N\u2010terminally truncated\u2010 and pyroglutamate\u2010modified amyloid peptide species (ADan and ABri), but that ADan peptides in FDD are also extensively C\u2010terminally truncated as compared to ABri in FBD, which contributes to hydrophobicity of ADan species. Further, CAA in FDD showed co\u2010deposition with A\u03b2 x\u201042 and A\u03b2 x\u201040 species. CAA+ vessels were structurally more mature than FDD\/FBD CAA and contained significant amounts of pyroglutamated A\u03b2. When compared with FDD, A\u03b2 in CAA+ showed more C\u2010terminal and less N\u2010terminally truncations. In FDD, ADan showed spatial co\u2010localization with A\u03b23pE\u201040 and A\u03b23\u201040 but not with A\u03b2x\u201042 species. This suggests an increased aggregation propensity of A\u03b2 in FDD that promotes co\u2010aggregation of both A\u03b2 and ADan. Further, CAA maturity appears to be mainly governed by A\u03b2 content based on the significantly higher 500\/580 patterns observed in CAA+ than in FDD and FBD, respectively. Together this is the first study of its kind on comprehensive delineation of Bri2 and APP\u2010derived amyloid peptides in single vascular plaques in both FDD\/FBD and sporadic CAA that provides new insight in non\u2010AD\u2010related vascular amyloid pathology.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15694-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>Cover Image for this issue: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15424\">https:\/\/doi.org\/10.1111\/jnc.15424<\/jats:ext-link><\/jats:p>","DOI":"10.1111\/jnc.15694","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T09:48:39Z","timestamp":1663148919000},"page":"233-246","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Chemical traits of cerebral amyloid angiopathy in familial British\u2010, Danish\u2010, and <scp>non\u2010Alzheimer<\/scp>\u02bcs dementias"],"prefix":"10.1111","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-3604","authenticated-orcid":false,"given":"Wojciech","family":"Michno","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Sahlgrenska Academy, University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Department of Neuroscience, Physiology and Pharmacology University College London  London UK"},{"name":"Department of Pediatrics, Stanford University School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Koutarapu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Sahlgrenska Academy, University of Gothenburg  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2325-6407","authenticated-orcid":false,"given":"Rafael","family":"Camacho","sequence":"additional","affiliation":[{"name":"Center for Cellular Imaging, Core Facilities The Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Toomey","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease Queen Square Institute of Neurology, University College London  London UK"},{"name":"Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences Queen Square Institute of Neurology, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Stringer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Sahlgrenska Academy, University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Department of Neuroscience, Physiology and Pharmacology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Minta","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Sahlgrenska Academy, University of Gothenburg  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyue","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Sahlgrenska Academy, University of Gothenburg  M\u00f6lndal 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