{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T03:23:44Z","timestamp":1785727424710,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,1]]},"group-title":"Neuroscience","reference-count":35,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103449"],"award-info":[{"award-number":["P20GM103449"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>According to the prevalent \u2018Amyloid Hypothesis,\u2019 the underlying cause for neurodegeneration in Alzheimer Disease (AD) is attributed to the accumulation of misfolded Amyloid \u00df and tau protein in the form of extracellular sticky plaques and neurofibrillary tangles respectively. These protein accumulations are thought to be caused by impaired waste removal. In an alternative hypothesis, we have proposed the existence of an extensive glial canal system that is likely formed by myelinated aquaporin-4 (AQP4)-expressing tanycytes and removes cellular waste from the hippocampal formation. Here, we demonstrate that tanycyte-derived waste-internalizing receptacles are immunoreactive for A\u00df and emanate from specialized nucleus-like organelles in the following referred to as \u2018tanysomes.\u2019 Utilizing RNA-scope in situ hybridization, we demonstrate that these receptacle-forming \u2018tanysomes\u2019 express RNA for AQP4 and the A\u00df-related genes, amyloid precursor protein, and presenilin 1. These findings suggest that A\u00df is likely synthesized where receptacle formation is observed and that A\u00df may play an important structural role in receptacle formation. In AD-affected hippocampus excessive amounts of A\u00df-immunoreactive waste receptacles emerge from tanysomes and have the appearance of plaques in A\u00df-immunolabeled hippocampus. Moreover, we demonstrate that the same receptacle-forming organelles exhibit strong immunolabeling for hyperphosphorylated tau protein in AD-affected tissue. We postulate that both proteins may play important structural roles in waste uptake and that hypertrophic swelling of impaired tanycytes in AD-affected brain may be due to obstructions of this extensive interconnected glial canal system.<\/jats:p>","DOI":"10.1101\/2025.06.01.657219","type":"posted-content","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T04:15:31Z","timestamp":1748837731000},"source":"Crossref","is-referenced-by-count":2,"title":["Uncovering the invisible giant: Amyloid \u00df plaques and their proposed association with waste removal in Alzheimer-affected human hippocampus"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1809-8291","authenticated-orcid":false,"given":"Ruth","family":"Fabian-Fine","sequence":"first","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail G.","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie J.","family":"Winters","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyleena J.","family":"Lathram","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly H.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luwago K.","family":"Kipingi","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sondre M.","family":"Br\u00e4nnare-Gran","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail E","family":"Whitley","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe M.","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia M.","family":"Altman","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn M.","family":"Joyce","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia A.","family":"Kragh","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore J.","family":"McKnight","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calum J.","family":"Reding","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Michael\u2019s College, Colchester, VT 05439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leaf J. 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