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Sequential deposition of post\u2010translationally modified A\u03b2<\/jats:italic> in plaques characterizes distinct biochemical stages of A\u03b2<\/jats:italic> maturation. However, the molecular composition of vascular A\u03b2<\/jats:italic> deposits in CAA and its relation to plaques remain enigmatic.<\/jats:p><\/jats:sec>Methods<\/jats:title>Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated A\u03b2<\/jats:italic> in the medial temporal and occipital lobe of 24 controls, 27 pathologically\u2010defined preclinical AD<\/jats:styled-content>, and 20 symptomatic AD<\/jats:styled-content> cases.<\/jats:p><\/jats:sec>Results<\/jats:title>Sequential deposition of A\u03b2<\/jats:italic> in CAA<\/jats:styled-content> resembled A\u03b2<\/jats:italic> maturation in plaques and enabled the distinction of three biochemical stages of CAA<\/jats:styled-content>. B\u2010CAA<\/jats:styled-content> stage 1 was characterized by deposition of A\u03b2<\/jats:italic> in the absence of pyroglutaminated A\u03b2<\/jats:italic>N3pE<\/jats:sub> and phosphorylated A\u03b2<\/jats:italic>pS8<\/jats:sub>. B\u2010CAA<\/jats:styled-content> stage 2 showed additional A\u03b2<\/jats:italic>N3pE<\/jats:sub> and B\u2010CAA<\/jats:styled-content> stage 3 additional A\u03b2<\/jats:italic>pS8<\/jats:sub>. Based on the A\u03b2<\/jats:italic> maturation staging in CAA<\/jats:styled-content> and plaques, three case groups for A\u03b2<\/jats:italic> pathology could be distinguished: group 1 with advanced A\u03b2<\/jats:italic> maturation in CAA<\/jats:styled-content>; group 2 with equal A\u03b2<\/jats:italic> maturation in CAA<\/jats:styled-content> and plaques; group 3 with advanced A\u03b2<\/jats:italic> maturation in plaques. All symptomatic AD<\/jats:styled-content> cases presented with end\u2010stage plaque maturation, whereas CAA<\/jats:styled-content> could exhibit immature A\u03b2<\/jats:italic> deposits. Notably, A\u03b2<\/jats:italic> pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia.<\/jats:p><\/jats:sec>Interpretation<\/jats:title>Balance of A\u03b2<\/jats:italic> maturation in CAA<\/jats:styled-content> and plaques defines distinct pathological subgroups of \u03b2<\/jats:italic>\u2010amyloidosis. The association of CAA<\/jats:styled-content>\u2010related A\u03b2<\/jats:italic> maturation with cognitive decline, the individual contribution of CAA<\/jats:styled-content> and plaque pathology to the development of dementia within the defined A\u03b2<\/jats:italic> pathology subgroups, and the subgroup\u2010related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.577","type":"journal-article","created":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T06:21:16Z","timestamp":1528352476000},"page":"815-831","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Modified amyloid variants in pathological subgroups of \u03b2<\/i>\u2010amyloidosis"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8100-6479","authenticated-orcid":false,"given":"Janina","family":"Gerth","sequence":"first","affiliation":[{"name":"Department of Neurology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajeet","family":"Rijal Upadhaya","sequence":"additional","affiliation":[{"name":"Laboratory for Neuropathology Institute for Pathology University of Ulm Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estifanos","family":"Ghebremedhin","sequence":"additional","affiliation":[{"name":"Department of Anatomy University of Frankfurt Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A. 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