{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:21:30Z","timestamp":1789147290218,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["24K17847"],"award-info":[{"award-number":["24K17847"]}]},{"name":"JSPS KAKENHI","award":["24K10554"],"award-info":[{"award-number":["24K10554"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The choroid plexus (CP) has traditionally been regarded as a cerebrospinal fluid-producing structure; however, increasing evidence indicates that it functions as a dynamic regulatory interface involved in immune surveillance, metabolic homeostasis, and brain clearance. Neuroimaging studies consistently report CP enlargement across aging and diverse neurological and neuropsychiatric disorders, yet the underlying cellular mechanisms remain poorly integrated. In this review, we synthesize morphological, molecular, and imaging evidence to propose a sequential degenerative model of the CP epithelium. This model comprises: (1) regulated epithelial cell loss via apical extrusion, (2) compensatory hypertrophy of residual cells, (3) mitochondrial remodeling with oncocytic-like change, and (4) progressive blood\u2013cerebrospinal fluid barrier dysfunction. At the molecular level, alterations in epithelial adhesion systems\u2014particularly SPINT1-mediated protease regulation and E-cadherin\u2013based adherens junction stability\u2014may initiate epithelial instability. Hypertrophic epithelial cells exhibit increased mitochondrial burden, reflected by Tom20 expression, which may initially support metabolic adaptation but ultimately contribute to oxidative stress and functional decline. At the macroscopic level, the cumulative effects of cell loss, hypertrophy, and mitochondrial remodeling likely underlie CP enlargement detectable by magnetic resonance imaging. This framework positions CP enlargement as an imaging-visible manifestation of epithelial stress and provides a structural\u2013molecular basis for interpreting CP alterations in brain aging and neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms27052505","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:27:18Z","timestamp":1773062838000},"page":"2505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Morphological and Molecular Characteristics of Choroid Plexus Epithelium in Aged Brains"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1902-7897","authenticated-orcid":false,"given":"Ryuta","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-3573","authenticated-orcid":false,"given":"Masaki","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Takamatsu 761-0793, Kagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/nrn3921","article-title":"Development and functions of the choroid plexus-cerebrospinal fluid system","volume":"16","author":"Lun","year":"2015","journal-title":"Nat. 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