{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:29:00Z","timestamp":1787840940119,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Positive \u03b1\u2010synuclein seed amplification assay (SAA) is a biomarker found in most people with Parkinson's disease (PD). We explored if free\u2010water (FW) imaging detects microstructural differences in the brains of patients with early PD with SAA+ or SAA\u2013 status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied patients with PD with baseline diffusion imaging and \u03b1\u2010synuclein SAA data from the Parkinson's Progression Markers Initiative (PPMI). We compared FW, FW corrected fractional anisotropy (FA\n                      <jats:sub>T<\/jats:sub>\n                      ), and clinical characteristics between SAA+ and SAA\u2013 groups. We also applied the Automated Imaging Differentiation for Parkinsonism (AIDP) at baseline to classify PD versus atypical parkinsonism, stratified by SAA status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 462 participants (41 SAA\u2013 and 421 SAA+), individuals with SAA+ had hyposmia and shorter motor symptom duration before baseline magnetic resonance imaging (MRI). AIDP identified PD in 92.4% (n\u2009=\u2009427, 91.6% had SAA+) and classified 7.6% as atypical parkinsonism (n\u2009=\u200935, 85.7% had SAA+). At baseline, SAA+ individuals had lower FW in the superior cerebellar peduncle, compared to SAA\u2013 (pFDR &lt;\u20090.05). No significant differences in FA\n                      <jats:sub>T<\/jats:sub>\n                      were found between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>\n                      Positive \u03b1\u2010synuclein SAA was associated with focal microstructural differences but did not distinguish broader diffusion MRI (dMRI) changes across FW and FA\n                      <jats:sub>T<\/jats:sub>\n                      metrics. These findings indicate that molecular confirmation of synuclein aggregation (via SAA) provides limited stratification of neurodegeneration detected by FW imaging in early PD. ANN NEUROL 2026;100:295\u2013304\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78252","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:52:42Z","timestamp":1778154762000},"page":"295-304","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Diffusion\n                    <scp>MRI<\/scp>\n                    and \u03b1\u2010Synuclein Seed Amplification Status in Parkinson's Disease"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-9867","authenticated-orcid":false,"given":"Shannon Y.","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic College of Medicine  Scottsdale AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010en","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology 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