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Characterization of age versus neuropathology\u2010associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology\u2013associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet,\n                      <jats:italic>Chlorocebus aethiops sabaeus<\/jats:italic>\n                      ), a well\u2010described model of early AD\u2010like neuropathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (A\u03b2) plaque load in parietal and temporal cortex was determined by immunohistochemistry, and concentrations of A\u03b242, A\u03b240, and norepinephrine in ITC were determined by enzyme\u2010linked immuosorbent assay (ELISA). Transcriptional profiles were compared between middle\u2010aged and old animals, and associations with AD\u2010relevant neuropathological measures were determined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptional profiles varied by brain region and age group. Expression levels of\n                      <jats:italic>TRO<\/jats:italic>\n                      and\n                      <jats:italic>RNU4\u20101<\/jats:italic>\n                      were significantly lower in all four regions in the older group. An additional 29 genes were differentially expressed by age in three of four regions. Analyses of a combined expression data set of all four regions identified 77 differentially expressed genes (DEGs) by age group. Among these DEGs, older subjects had elevated levels of\n                      <jats:italic>CTSB<\/jats:italic>\n                      <jats:italic>, EBAG9<\/jats:italic>\n                      ,\n                      <jats:italic>LAMTOR3<\/jats:italic>\n                      , and\n                      <jats:italic>MRPL17<\/jats:italic>\n                      , and lower levels of\n                      <jats:italic>COMMD10<\/jats:italic>\n                      and\n                      <jats:italic>TYW1B<\/jats:italic>\n                      . A subset of these DEGs was associated with neuropathology biomarkers. Notably,\n                      <jats:italic>CTSB<\/jats:italic>\n                      was positively correlated with A\u03b2 plaque counts, A\u03b242:A\u03b240 ratios, and norepinephrine levels in all brain regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These data demonstrate age differences in gene expression in olfaction\u2010associated brain regions. Biological processes exhibiting age\u2010related enrichment included the regulation of cell death, vascular function, mitochondrial function, and proteostasis. A subset of DEGs was specifically associated with AD phenotypes. These may represent promising targets for future mechanistic investigations and perhaps therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12358","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T08:23:37Z","timestamp":1666859017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transcriptional profiles in olfactory pathway\u2013associated brain regions of African green monkeys: Associations with age and Alzheimer's disease neuropathology"],"prefix":"10.1002","volume":"8","author":[{"given":"Jacob D.","family":"Negrey","sequence":"first","affiliation":[{"name":"Department of Pathology\/Comparative Medicine Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy L.","family":"Dobbins","sequence":"additional","affiliation":[{"name":"Department of 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Anesthesiology University of Illinois  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas L.","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Illinois  Chicago Illinois USA"},{"name":"Research and Development Jesse Brown VA Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Gerontology and Geriatric Medicine Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"},{"name":"Wake Forest Alzheimer's Disease Research Center  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A.","family":"Shively","sequence":"additional","affiliation":[{"name":"Department of Pathology\/Comparative Medicine Wake Forest School of Medicine  Winston\u2010Salem North Carolina 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