{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:41:18Z","timestamp":1778618478920,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG062677"],"award-info":[{"award-number":["P30AG062677"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01NS100620"],"award-info":[{"award-number":["U01NS100620"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007451","name":"Cell Science Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007451","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Increasing evidence indicates that \u03b1\u2010synuclein (\u03b1SYN) oligomers are toxic. We sought to determine whether \u03b1SYN oligomers were associated with faster cognitive decline in prospectively\u2010followed patients with dementia with Lewy bodies (DLB).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Eight autopsy\u2010confirmed patients with DLB were selected based on rapid or slow cognitive decline determined by the rate of change of Mini\u2010Mental State Examination (MMSE) scores. Quantitative neuropathologic analysis of \u03b1SYN oligomers, Lewy\u2010related pathology, phosphorylated tau, and amyloid\u2010\u03b2 was conducted in hippocampal subfields (CA1\u20104 and subiculum) and the entorhinal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>DLB with rapid cognitive decline showed greater CA1 \u03b1SYN oligomer burden (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.029) and tau burden (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.029) than DLB with slow decline. The groups showed comparable burden of Lewy\u2010related pathology and amyloid\u2010\u03b2 pathology in the hippocampal formation and entorhinal cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Hippocampal accumulation of \u03b1SYN oligomers and phosphorylated tau is associated with rapid cognitive decline in DLB. Therapeutic strategies targeting \u03b1SYN oligomers warrant further investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Proximity ligation assay (PLA) and digital pathology for oligomer quantification.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Abundant \u03b1\u2010synuclein (\u03b1SYN) oligomers in CA1 of patients with dementia with Lewy bodies (DLB) with rapid decline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>First human brain study linking \u03b1SYN oligomers to cognitive trajectory.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Potential therapeutic implications of targeting \u03b1SYN oligomers in DLB.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70374","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T07:31:11Z","timestamp":1754292671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of hippocampal \u03b1\u2010synuclein oligomers on cognitive trajectory in patients with dementia with Lewy bodies"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-5966","authenticated-orcid":false,"given":"Hiroaki","family":"Sekiya","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Franke","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"DeTure","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Owen A.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa E.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela J.","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanis J.","family":"Ferman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Psychology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Jacksonville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004058"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0852-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009258"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00501-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14808"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/416507a"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100976108"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.037"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv040"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-01961-w"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01440-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12844"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70156-9"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11067-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000210021"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02255-2"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29670"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.09.014"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.07.004"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-025-02872-9"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab092"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1755-1"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1443"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511256103"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30291-5"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009763"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2028-17.2017"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00021-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31825018f7"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jagp.2015.06.006"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12659"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209460"}],"container-title":["Alzheimer's &amp; 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