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We aimed to evaluate the effects of amyloid beta (A\u03b2), tau, and Lewy body (LB) pathologies on NPS in A\u03b2\u2010positive individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In 336 A\u03b2\u2010positive participants from the Alzheimer's Disease Neuroimaging Initiative cohort, spanning from cognitively unimpaired to those with early dementia, NPS were assessed. A\u03b2 and tau positron emission tomography were conducted. In a subgroup of 238 participants, dichotomized LB pathology was assessed by detecting \u03b1\u2010synuclein seeding activity. The effects of A\u03b2, tau, and LB pathologies on NPS were evaluated using logistic regression analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Greater tau burden was associated with delusion, agitation\/aggression, irritability\/lability, aberrant motor behavior, and appetite\/eating disorder. In subgroup analyses, LB pathology was associated with delusion, anxiety, apathy, and sleep disturbance, independent of A\u03b2 and tau burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Tau and LB pathologies are major determinants of NPS in A\u03b2\u2010positive individuals, each contributing distinct symptom profiles.<\/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>Tau burden was associated with delusion, agitation\/aggression, irritability\/lability, aberrant motor behavior, and appetite\/eating disorder.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tau in frontal, temporal, and limbic cortices was associated with delusion.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In amyloid beta (A\u03b2)\u2013positive individuals, co\u2010occurring Lewy body (LB) pathology is associated delusion, anxiety, apathy, and sleep disturbance, independent of tau.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tau and LB pathologies are associated with the distinct profiles of neuropsychiatric symptoms in A\u03b2\u2010positive individuals.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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