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Interactions with cerebrospinal fluid (CSF) AD biomarkers were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>SAA+ was associated with widespread hypometabolism among CI individuals, particularly in posterior cortical regions, independent of CSF amyloid and tau levels in the occipital lobes. Regional hypometabolism mediated the effect of \u03b1\u2010syn SAA on disease severity in CI individuals, independent of CSF amyloid and tau levels. There were no influences of SAA on FDG\u2010PET in CU individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study supports a model in which \u03b1\u2010syn aggregation influences metabolic dysfunction, which then influences clinical disease severity, independent of AD. SAA+ could help optimize participant selection and outcome measures for clinical trials in 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>\u03b1\u2010synuclein seed amplification positivity (SAA+) was associated with hypometabolism in cognitively impaired individuals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Hypometabolism mediated the influence of \u03b1\u2010synuclein on disease severity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Occipital hypometabolism in SAA+ was independent of cerebrospinal fluid levels of Alzheimer's disease pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings can optimize future clinical trials targeting \u03b1\u2010synuclein pathology.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14571","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T03:50:31Z","timestamp":1739332231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Influence of alpha\u2010synuclein on glucose metabolism in Alzheimer's disease continuum: Analyses of \u03b1\u2010synuclein seed amplification assay and FDG\u2010PET"],"prefix":"10.1002","volume":"21","author":[{"given":"Elijah","family":"Mak","sequence":"first","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department 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