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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is an unremitting neurodegenerative disorder characterized by the presence of extracellular \u03b2-amyloid (A\u03b2)-containing neuritic plaques, intracellular tau-positive neurofibrillary tangles and loss of selected neurons in the brain. Evidence suggests that aggregation of A\u03b2 and tau via synergistic interactions initiates a cascade of events, leading to development of AD pathology. Thus, many studies are being pursued to develop small molecules\/drugs that can target both A\u03b2 and tau as an effective AD treatment strategy. In this study, we evaluated effects of native PLGA nanoparticles on tau-mediated A\u03b21-42 aggregation using biophysical, structural, spectroscopic and biochemical approaches. Our results show that 0N4R tau seeds enhanced A\u03b21-42 aggregation, and that this effect is mitigated by native PLGA. Additionally, PLGA inhibited A\u03b21-42 aggregation induced by both 0N4R and 2N4R tau isoforms. The presence of PLGA during the formation of tau seeds or pretreatment of tau seeds with PLGA attenuates subsequent A\u03b21-42 aggregation. Interestingly, monomeric 0N4R tau, unlike 0N4R tau seeds, suppressed A\u03b21-42 aggregation, which is diminished further by PLGA nanoparticles. However, we have not addressed the implications of native PLGA on tau\/A\u03b21-42 interaction using any cellular or animal models of AD. Nevertheless, our results reveal that tau seeds and monomeric tau can differentially influence A\u03b21-42 aggregation, which is mitigated by native PLGA under in vitro conditions, providing a rationale to study it further under an in vivo paradigm to examine its significance in AD pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms27188152","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"8152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Attenuation of Tau-Mediated \u03b2-Amyloid1-42 Aggregation by Native PLGA Nanoparticles and Its Relevance to Alzheimer Disease Pathology"],"prefix":"10.3390","volume":"27","author":[{"given":"Pallabi Sil","family":"Paul","sequence":"first","affiliation":[{"name":"Department of Medicine (Neurology), Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliza","family":"Borenstein-Katz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6361-9679","authenticated-orcid":false,"given":"Klinton","family":"Shmeit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-8706","authenticated-orcid":false,"given":"Holger","family":"Wille","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyabrata","family":"Kar","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada"},{"name":"Department of Psychiatry, Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/ene.13439","article-title":"Alzheimer\u2019s disease","volume":"25","author":"Lane","year":"2018","journal-title":"Eur. 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