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Genetic risk factors may drive mixed pathology presentation, but their influence on the development of specific co\u2010pathologies remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We evaluated the\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      coding variant rs3173615 and apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      )\u00a0diplotype (rs429358, rs7412) in\n                      <jats:italic>post mortem<\/jats:italic>\n                      brains from 2604 individuals with a primary neuropathologic diagnosis of AD. Binary logistic regression models linked each genetic modifier with co\u2010pathology risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      risk variant was significantly enriched in AD cases with transactive response DNA\u2010binding protein 43 kDa (TDP\u201043) pathology \u2013 associating with increased odds of developing AD TDP\u201043 subtype \u03b1 \u2013 but failed to associate with Lewy body or vascular pathology. In contrast,\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 associated with increased risk for multiple co\u2010pathologies in AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      We find that genetic factors individually influence AD pathological heterogeneity:\n                      <jats:italic>TMEM106B<\/jats:italic>\n                      selectively modulates TDP\u201043 co\u2010pathology, while\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 appears broadly permissive to co\u2010pathology development.\n                    <\/jats:p>\n                  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