{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:26:27Z","timestamp":1777397187916,"version":"3.51.4"},"reference-count":66,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100005423","name":"Akademiska Sjukhuset","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005423","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hans Gabriel and Alice Trolle-Wachtmeister Foundation."}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In aging-related neurodegeneration, therapeutic interventions directed at defined protein targets have been launched. A key step has been developing diagnostic biological markers, followed by immunotherapy. These steps have been achieved for amyloid-\u03b2 protein (A\u03b2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate, based on brain pathology, how frequently A\u03b2 would be detectable in blood or cerebrospinal fluid in older individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed brain tissue from 1825 deceased subjects, 20% of whom were demented. We examined the presence of A\u03b2, hyperphosphorylated \u03c4 (HP\u03c4), Transactive DNA-binding protein 43 (TDP-43), and \u03b1-synuclein (\u03b1S) using immunohistochemistry. The extent of these alterations was assessed following current consensus criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The combination of A\u03b2\/HP\u03c4, constituting Alzheimer's disease neuropathological change (ADNC), was detected in 64% of subjects, increasing significantly (Pearson's Chi-Square\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.001) from 46% in the 5\n                      <jats:sup>th<\/jats:sup>\n                      decade to 81% in the 9\n                      <jats:sup>th<\/jats:sup>\n                      decade. In 506 subjects (28% of the cohort), intermediate or high levels of ADNC were observed an extent reported as assessable in cerebrospinal fluid. Among these, 235 were non-demented and would have been identified as being at risk of Alzheimer's disease. Most (74%) displayed concomitant pathologies, making it impossible at this stage to determine which pathology will eventually lead to cognitive impairment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Common ADNC and frequent concomitant pathologies in older individuals will influence the interpretation of diagnostic biological tests. Current tests can confirm that a subject displays ADNC; however, a definite diagnosis can only be achieved through postmortem neuropathological assessment. Present diagnostic tests are too crude to detect early or low-level ADNC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251414978","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T13:08:47Z","timestamp":1770210527000},"page":"397-408","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Incidence of altered proteins in the aging brain: Implications for biological diagnostic markers"],"prefix":"10.1177","volume":"110","author":[{"given":"Irina","family":"Alafuzoff","sequence":"first","affiliation":[{"name":"Department of Pathology, Uppsala University Hospital, Uppsala, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylwia","family":"Libard","sequence":"additional","affiliation":[{"name":"Department of Pathology, Uppsala University Hospital, Uppsala, Sweden"},{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-1800756"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1962.04210030065009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00430862"},{"key":"e_1_3_3_5_2","first-page":"357","article-title":"The amyloid deposits in Alzheimer's disease: their nature and pathogenesis","volume":"2","author":"Glenner GG","year":"1984","unstructured":"Glenner GG, Wong CW, Quaranta V, et al. 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