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Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD), primary age\u2010related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p\u2010tau)\u2013immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (A\u03b2) deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)\u2010bearing and non\u2013NFT\u2010bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy\u2010confirmed AD (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a08), PART (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\u00a07), and CTE (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>There were numerous subregion\u2010specific differences related to A\u03b2 processing, autophagy\/proteostasis, inflammation, gliosis, oxidative stress, neuronal\/synaptic integrity, and p\u2010tau epitopes among these different disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results suggest that there are subregion\u2010specific proteomic differences among the neurons of these disorders, which appear to be influenced to a large degree by the presence of hippocampal A\u03b2. These proteomic differences may play a role in the differing hippocampal p\u2010tau distribution and pathogenesis of these disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Alzheimer's disease neuropathologic change (ADNC), possible primary age\u2010related tauopathy (PART), definite PART, and chronic traumatic encephalopathy (CTE) can be differentiated based on the proteomic composition of their neurofibrillary tangle (NFT)\u2010 and non\u2013NFT\u2010bearing neurons.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The proteome of these NFT\u2010 and non\u2013NFT\u2010bearing neurons is largely correlated with the presence or absence of amyloid beta (A\u03b2).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Neurons in CTE and definite PART (A\u03b2\u2010independent pathologies) share numerous proteomic similarities that distinguish them from ADNC and possible PART (A\u03b2\u2010positive pathologies).<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14487","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T06:44:56Z","timestamp":1735627496000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age\u2010related tauopathy hippocampi"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7068-5517","authenticated-orcid":false,"given":"Timothy E.","family":"Richardson","sequence":"first","affiliation":[{"name":"Department of Pathology Molecular, and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda E.","family":"Orr","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"St. Louis VA Medical Center  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy C.","family":"Orr","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Rohde","sequence":"additional","affiliation":[{"name":"Department of Pathology Molecular, and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Pathology Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Neuroscience Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Human Genetics Genomics of Neurodegenerative Diseases and Aging Vrije Universiteit Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Neurology Alzheimer Center Amsterdam Neuroscience Vrije Universiteit Amsterdam  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Ehrenberg","sequence":"additional","affiliation":[{"name":"Memory and Aging Center Weill Institute for Neurosciences University of California  San Francisco California USA"},{"name":"Helen Wills Neuroscience Institute University of California  Berkeley California USA"},{"name":"Innovative Genomics Institute University of California  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Thorn","sequence":"additional","affiliation":[{"name":"Department of Pathology Molecular, and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Neuropathology Brain Bank &amp; Research CoRE Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Christie","sequence":"additional","affiliation":[{"name":"Department of Pathology Molecular, and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Neuropathology Brain Bank &amp; Research CoRE Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Flores\u2010Almazan","sequence":"additional","affiliation":[{"name":"Department of Pathology Molecular, and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Neuropathology Brain Bank &amp; Research CoRE Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robina","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Pathology Molecular, and Cell\u2010Based Medicine Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Neuropathology Brain Bank &amp; 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Research CoRE Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Nash Family Department of Neuroscience Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Artificial Intelligence &amp; Human Health Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Ronald M. 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