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The primary objective of the present study was to validate these findings in the APP\/PS1 mouse model using a larger cohort of animals. A second objective was to determine whether PAA binds directly to amyloid plaques in brain tissue sections.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    For the\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies, APP\/PS1 mice received daily oral PAA or vehicle treatment and were euthanized at one year of age. Brains were collected, fixed, cryosectioned, and stained with hydroxyquinoline oxalate (HQ-O) to visualize amyloid plaques. For the\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies, brain tissue sections were incubated in a PAA solution. Double labeling with PAA and HQ-O was performed on the same tissue sections to compare plaque labeling patterns.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Daily oral administration of PAA produced a significant reduction in both the number and size of amyloid plaques compared with untreated control mice. In vitro incubation of tissue sections with PAA resulted in red fluorescent labeling of all amyloid plaques. Double-labeling studies showed that PAA labeled plaques are more extensive than HQ-O in frozen tissue sections, whereas no such difference was observed in paraffin-embedded sections.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings extend our previous observation that chronic oral administration of PAA significantly reduces amyloid plaque burden in vivo. In addition, the in vitro studies demonstrate that PAA binds directly to amyloid plaques. The mechanism of PAA binding may involve interactions with transition metals incorporated within amyloid plaques and\/or the sialic acid moieties of plaque-associated gangliosides.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.27.740397","type":"posted-content","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:50:13Z","timestamp":1785430213000},"source":"Crossref","is-referenced-by-count":0,"title":["Oral administration of 1,10-phenanthroline-5-amine (PAA) significantly reduced amyloid plaque burden compared with untreated APP\/PS1 mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3666-7099","authenticated-orcid":false,"given":"Larry","family":"Schmued","sequence":"first","affiliation":[{"name":"Histo-Chem Inc, White Hall, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2364-9649","authenticated-orcid":false,"given":"Bryan","family":"Maloney","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvert","family":"Schmued","sequence":"additional","affiliation":[{"name":"Histo-Chem Inc, White Hall, AR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Gregerson","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-5933","authenticated-orcid":false,"given":"Debomoy K.","family":"Lahiri","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry"},{"name":"Departments of Medical & Molecular Genetics, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indian Alzheimer\u2019s Disease Research Center, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"4","key":"2026080212250515000_2026.07.27.740397v1.1","doi-asserted-by":"crossref","first-page":"e70235","DOI":"10.1002\/alz.70235","article-title":"2025 Alzheimer\u2019s disease facts and figures","volume":"21","author":"Alzheimer\u2019s Association","year":"2025","journal-title":"Alzheimer\u2019s & Dementia"},{"key":"2026080212250515000_2026.07.27.740397v1.2","unstructured":"World Health Organization. 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