{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:05:40Z","timestamp":1785297940836,"version":"3.55.0"},"reference-count":71,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) occurs primarily as late\u2011onset (LOAD) and less frequently as early\u2011onset (EOAD). Its defining pathologies are hyperphosphorylated tau tangles and amyloid beta (A\u03b2) plaques.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We analyzed the proteomes of 115\n                      <jats:italic>post mortem<\/jats:italic>\n                      temporal lobe samples by mass spectrometry and searched with a dedicated AD spectral library including tau post\u2011translational modifications and A\u03b2 isoforms to examine global protein changes in LOAD and EOAD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>AD tissues showed mitochondrial and synaptic pathway downregulation and immune and small\u2011molecule metabolic process upregulation, with EOAD exhibiting larger fold changes. AD biomarkers were elevated, and two multi\u2011phosphorylated tau peptides (p\u2011tau231\/p\u2010tau235 and p\u2010tau231\/p\u2010tau235\/p\u2010tau237) were detected predominantly in AD. A\u03b2 was present in 45% of cognitively unimpaired elderly controls, with subtle proteome changes resembling an early stage of neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>EOAD appears more aggressive. Tau p\u2010tau231\/p\u2010tau235 and p\u2010tau231\/p\u2010tau235\/p\u2010tau237 hold promise as novel AD biomarkers. A\u03b2\u2019s detection in cognitively unimpaired elderly controls precedes clinical AD symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71662","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T03:36:16Z","timestamp":1783913776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteomics of post mortem brains in early\u2010 and late\u2010onset Alzheimer's disease: Unraveling differential A\u03b2 effects and potential AD biomarkers"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6843-4591","authenticated-orcid":false,"given":"Evangelia","family":"Thanou","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics &amp; Cognitive Research Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ganz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics &amp; Cognitive Research Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora","family":"Pita\u2010Illobre","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics &amp; Cognitive Research Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Koopmans","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics &amp; Cognitive Research Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J. M.","family":"Hoozemans","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"Rozemuller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Amsterdam Neuroscience Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henne","family":"Holstege","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam Neuroscience Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"August B.","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics &amp; Cognitive Research Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Wan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology, Center for Neurogenomics &amp; Cognitive Research Neuroscience Vrije Universiteit Amsterdam  Amsterdam The 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