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This study uses quantitative susceptibility mapping (QSM) to investigate links among brain iron, plasma neurodegenerative proteins, and cognition in CSVD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>This study enrolled 319 CSVD patients, grouped into CSVD\u2010M and CSVD\u2010S. Plasma proteins were measured in 178 participants, with 80 being followed up after 2 years. QSM\u2010based voxel\u2010wise analysis assessed brain iron, CSVD severity, and protein correlations. A cross\u2010lagged panel model was used to analyze the temporal association between plasma protein levels and brain iron levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In CSVD\u2010S, elevated QSM values in the right Rolandic operculum\/superior temporal gyrus negatively correlated with plasma A\u03b242 and executive function. A\u03b242 also negatively correlated with QSM in cortical regions, tied to episodic memory decline. Higher baseline A\u03b240 predicted increased QSM in the left putamen at follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Plasma A\u03b242 and A\u03b240 may drive brain iron deposition and cognitive impairment in CSVD, serving as potential early biomarkers for disease progression.<\/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>QSM reveals brain iron links to A\u03b242, cognition in CSVD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma A\u03b242 correlates with iron in motor and frontal areas.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>High A\u03b240 predicts putamen iron increase in CSVD follow\u2010up.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Iron deposition is tied to executive, memory deficits in CSVD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70710","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T03:04:44Z","timestamp":1759201484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Associations of neurodegenerative proteins with brain iron deposition and cognition in cerebral small vessel disease: a quantitative susceptibility mapping and plasma biomarker study"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9411-0145","authenticated-orcid":false,"given":"Yiwen","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education, Department of Radiology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8320-5241","authenticated-orcid":false,"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Jena University Hospital  Jena Thuringia Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-6600","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Tsinghua Changgung 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