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multimodal analysis involving descriptive statistics, multifactorial regression, mediation analysis, and receiver operating characteristic curve assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>LC degenerative changes (18.57%) significantly exceeded SN changes (4.69%). The LC demonstrated stronger correlations with psychiatric symptoms and cognitive impairment. High LC\/low SN damage patterns showed the strongest associations with mild cognitive impairment (OR\u00a0=\u00a02.38) and AD (OR\u00a0=\u00a03.56).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our research reveals the heterogeneous degeneration patterns of LC and SN in AD, providing crucial insights into neurobiological mechanisms and potential strategies for early diagnosis and intervention.<\/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>This study provides a comprehensive framework for understanding the heterogeneous neurodegeneration patterns in AD through a detailed examination of the LC and SN.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The research bridges the gap between neuroanatomical changes and neuropsychiatric symptoms, offering a more nuanced perspective on disease progression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our findings challenge traditional linear models of neurodegeneration, emphasizing the complex and non\u2010uniform nature of neural deterioration in AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The study underscores the critical importance of investigating multiple neural nuclei to comprehensively understand neurodegenerative processes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>By exploring the differential vulnerabilities of LC and SN, we provide new insights into potential targeted therapeutic interventions.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70605","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T07:54:57Z","timestamp":1756799697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unraveling the complexity of neurodegeneration: heterogeneous damage patterns of locus coeruleus and substantia nigra in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Chao","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Guizhou Medical University  Guiyang Guizhou Province 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