{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:57:23Z","timestamp":1781798243696,"version":"3.54.5"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech and App Biochem"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by the pathological aggregation of specific proteins such as amyloid beta (A\u03b2) and \u03b1\u2010synuclein, respectively. Early detection of these protein aggregates in biological fluids could facilitate timely diagnosis and therapeutic intervention. This study explores an aggregate amplification approach using the surface\u2010based fluorescence intensity distribution analysis (sFIDA) method to enhance the detection sensitivity of A\u03b2 and \u03b1\u2010synuclein seeds. Two amplification strategies were investigated: surface\u2010bound and solution\u2010phase amplification. In the case of A\u03b2, surface\u2010bound amplification using immobilized A\u03b2\u2010specific antibodies was tested with synthetic A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    seeds and monomeric A\u03b2\n                    <jats:sub>1\u201042<\/jats:sub>\n                    as the substrate. Despite observable aggregation, self\u2010aggregation of the monomeric substrate interfered with seed\u2010dependent amplification, rendering the approach ineffective at physiologically relevant concentrations. Attempts to suppress self\u2010aggregation using blocking peptides, bovine serum albumin, and truncated A\u03b2\n                    <jats:sub>11\u201042<\/jats:sub>\n                    substrates were unsuccessful. Solution\u2010phase amplification followed by surface detection also failed to reliably differentiate seeded aggregation from self\u2010aggregation, indicating that A\u03b2 amplification is unsuitable for diagnostic applications. In contrast, \u03b1\u2010synuclein exhibited significantly lower self\u2010aggregation, allowing for more effective seeded amplification. Surface\u2010bound \u03b1\u2010synuclein amplification successfully detected synthetic seeds at nanomolar concentrations, while solution\u2010phase amplification further improved sensitivity, enabling detection down to the picomolar range. The method was successfully applied to brain homogenates from transgenic PD model mice, demonstrating the potential for detecting \u03b1\u2010synuclein seeds in biological samples. These findings highlight the limitations of A\u03b2 amplification for diagnostic purposes while supporting the feasibility of \u03b1\u2010synuclein amplification for PD detection. Future work will focus on optimizing this approach for clinical applications.\n                  <\/jats:p>","DOI":"10.1002\/bab.70083","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T18:03:38Z","timestamp":1761933818000},"page":"1115-1124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Single Particles of Amyloid Beta and \u03b1\u2010Synuclein With Seeded Amplification for the Diagnosis of Alzheimer's and Parkinson's Disease"],"prefix":"10.1002","volume":"73","author":[{"given":"Alexandra","family":"Dybala","sequence":"first","affiliation":[{"name":"Mathematisch\u2010Naturwissenschaftliche Fakult\u00e4t, Institut f\u00fcr Physikalische Biologie Heinrich\u2010Heine\u2010Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene","family":"Pils","sequence":"additional","affiliation":[{"name":"attyloid GmbH  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Bannach","sequence":"additional","affiliation":[{"name":"attyloid GmbH  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6933-5154","authenticated-orcid":false,"given":"G\u00fcltekin","family":"Tamg\u00fcney","sequence":"additional","affiliation":[{"name":"Mathematisch\u2010Naturwissenschaftliche Fakult\u00e4t, Institut f\u00fcr Physikalische Biologie Heinrich\u2010Heine\u2010Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"},{"name":"Institute of Biological Information Processing (Structural Biochemistry: IBI\u20107) Forschungszentrum J\u00fclich  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlev","family":"Riesner","sequence":"additional","affiliation":[{"name":"Mathematisch\u2010Naturwissenschaftliche Fakult\u00e4t, Institut f\u00fcr Physikalische Biologie Heinrich\u2010Heine\u2010Universit\u00e4t D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06437-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-022-00410-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(84)80190-4"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.11.4044"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.12.4245"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00109-6"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02358-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac115"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-022-00330-x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-024-00690-w"},{"issue":"2","key":"e_1_2_10_15_1","article-title":"A\u03b2 Oligomers Peak in Early Stages of Alzheimer's Disease Preceding Tau Pathology","volume":"16","author":"Bl\u00f6meke L.","year":"2024","journal-title":"Alzheimer's & Dementia"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29923"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0333-7"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac333"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02869-z"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2016.11.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12983"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00458-4"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01597-3"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036620"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2013.05.021"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(20000215)59:4<528::AID-JNR8>3.0.CO;2-0"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210105200"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90140-6"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0502137"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.122093"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.11.016"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02037-5"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/2654"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05319-3"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12683-8"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm7285"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12465"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-240272"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12481"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19961-3"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20160868"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz6014"}],"container-title":["Biotechnology and Applied Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bab.70083","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bab.70083","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bab.70083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:46:14Z","timestamp":1781797574000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/bab.70083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/bab.70083"],"URL":"https:\/\/doi.org\/10.1002\/bab.70083","archive":["Portico"],"relation":{},"ISSN":["0885-4513","1470-8744"],"issn-type":[{"value":"0885-4513","type":"print"},{"value":"1470-8744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]},"assertion":[{"value":"2025-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}