{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:07:52Z","timestamp":1789560472635,"version":"build-2803163510"},"reference-count":75,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Greater white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are seen with transactive response DNA\u2010binding protein 43 (TDP\u201043) pathology in frontotemporal lobar degeneration (FTLD\u2010TDP). WMH associations with TDP\u201043 pathology in Alzheimer's disease (AD\u2010TDP) remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A total of 157 participants from Mayo Clinic Rochester with autopsy\u2010confirmed AD, known TDP\u201043 status, and antemortem fluid\u2010attenuated inversion recovery (FLAIR) MRI were included. Vascular risk factors were assessed. A semi\u2010automated WMH segmentation\u2010quantification process produced total and regional WMH volumes. Penalized linear regression models adjusting for age at MRI analyzed TDP\u201043 associations (status and typing) with WMHs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      TDP\u201043\u2010positive status was not associated with WMH burden overall because opposite effects were seen based on AD\u2010TDP typing. Despite similar antemortem vascular risk factors and postmortem vascular pathologies, AD\u2010TDP type\u2010\n                      <jats:italic>\u03b1<\/jats:italic>\n                      showed greater total and regional WMH burden (particularly in subcortical frontotemporal and basal ganglia regions) than TDP\u201043 negatives and AD\u2010TDP type\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      AD\u2010TDP types may have different WMH pathomechanisms, with type\u2010\n                      <jats:italic>\u03b1<\/jats:italic>\n                      having associations more like FTLD\u2010TDP than AD.\n                    <\/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>In transactive response DNA\u2010binding protein 43 (TDP\u201043) pathology in Alzheimer's disease (AD\u2010TDP), TDP\u201043 status alone is not associated with total or regional WMH burden<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            AD\u2010TDP type\u2010\n                            <jats:italic>\u03b1<\/jats:italic>\n                            shows greater total, frontotemporal subcortical, and basal ganglia white matter hyperintensities (WMHs)\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            AD\u2010TDP type\u2010\n                            <jats:italic>\u03b2<\/jats:italic>\n                            shows less total and subcortical occipital WMHs\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            AD\u2010TDP type\u2010\n                            <jats:italic>\u03b1<\/jats:italic>\n                            effect on WMH burden closely mimics the effects of frontotemporal lobar degeneration with TDP\u201043 (FTLD\u2010TDP) rather than AD\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Different relationships of AD\u2010TDP types with WMHs suggest different pathomechanisms<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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