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Single population RNA sequencing was conducted using tissue from subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. Differentially expressed genes (DEGs) were compared across groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>DEGs increased from prodromal (MCI vs. NCI) to progression (AD vs. MCI) to frank AD (AD vs. NCI). The majority of DEGs and pathways shared between prodromal and progression exhibited a change in the direction of dysregulation unlike pathways between progression and frank AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Candidate genes and pathways were identified that demarcate early\u2010stage AD onset from AD progression, providing a roadmap to study cortical cellular vulnerability and key targets for intervention at early stages of AD.<\/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>Pyramidal neuron differentially expressed genes (DEGs) are directionally divergent between prodromal, progression, and frank\u00a0Alzheimer's disease (AD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pyramidal neuron DEGs are directionally convergent between progression and frank AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Dysfunctional bioenergetic pathways increased dysregulation as the AD spectrum progressed.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Immune response pathways were more dysregulated in frank AD than prodromal stages.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>DEGs, = biological pathways, and interactomes\u00a0demarcate specific stages across the AD spectrum.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70395","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:22:56Z","timestamp":1753435376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Frontal cortex pyramidal neuron expression profiles differentiate the prodromal stage from progressive degeneration across the Alzheimer's disease spectrum"],"prefix":"10.1002","volume":"21","author":[{"given":"Amanda","family":"Labuza","sequence":"first","affiliation":[{"name":"Center for Dementia Research Nathan Kline Institute Orangeburg New York USA"},{"name":"Department of Psychiatry New York University Grossman School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Alldred","sequence":"additional","affiliation":[{"name":"Center for Dementia Research Nathan Kline Institute Orangeburg New 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