{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:54:20Z","timestamp":1777395260614,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2021,4,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Stepwise occurrence of biochemically modified amyloid-\u03b2 (A\u03b2) in the brain of subjects with Alzheimer\u2019s disease (AD) has been suggested to be of significance for cognitive impairment. Our previous reports have shown that A\u03b2 is observed in 63% of all subjects with idiopathic normal pressure hydrocephalus (iNPH) suggesting that the majority of iNPH subjects with A\u03b2 are indeed also suffering from AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We assessed the occurrence of biochemically modified A\u03b2 variants, in vivo, in subjects with iNPH and in a cohort of postmortem brain samples from patients with dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We assessed A\u03b2 proteins in 127 diagnostic brain biopsies obtained from subjects with iNPH and in a cohort of subjects with dementia by means of immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The pyroglutamylated A\u03b2 (pyA\u03b2) precedes the aggregation of phosphorylated A\u03b2 (pA\u03b2) during the AD neuropathological change progression; moreover, these modified variants of A\u03b2 correlate with hyperphosphorylated tau in the frontal cortical area of human brain. Our results confirm the existence of the suggested biochemical stages of A\u03b2 aggregation that might be of significance for neurodegeneration leading to cognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The observation that both pyA\u03b2 and pA\u03b2 are seen in vivo in iNPH subjects is intriguing. It has been reported that most of the iNPH subjects with A\u03b2 in the brain biopsy indeed develop AD with time. Based on our current and previous results, it is clinically merited to obtain a diagnostic biopsy from a subject with iNPH. When A\u03b2 is observed in the biopsy, the biochemical characterization is of interest.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-201469","type":"journal-article","created":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T12:00:35Z","timestamp":1613476835000},"page":"1003-1012","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>In vivo<\/i>\n                    Characterization of Biochemical Variants of Amyloid-\u03b2 in Subjects with Idiopathic Normal Pressure Hydrocephalus and Alzheimer\u2019s Disease Neuropathological Change"],"prefix":"10.1177","volume":"80","author":[{"given":"Sylwia","family":"Libard","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"},{"name":"Department of Pathology, Uppsala University Hospital, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Bonn, Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Alafuzoff","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uppsala University Hospital, Uppsala, 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