{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T02:13:12Z","timestamp":1778551992896,"version":"3.51.4"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to the treatment of neurodegenerative conditions, with a particular focus on Alzheimer\u2019s disease (AD). However, the mechanism that underlies regulation of GLP-1R availability in the brain with AD remains poorly understood. Here, using whole transcriptome RNA-Seq of the human postmortem caudate nucleus with AD and chronic hydrocephalus (CH) in the elderly, we found that GLP-1R and select mRNAs expressed in glucose dysmetabolism and dyslipidemia were significantly altered. Furthermore, we detected human RNA indicating a deficiency in doublecortin (DCX) levels and the presence of ferroptosis in the caudate nucleus impacted by AD. Using the genome data viewer, we assessed mutability of GLP-1R and 39 other genes by two factors associated with high mutation rates in chromosomes of four species. Surprisingly, we identified that nucleotide sizes of GLP-1R transcript exceptionally differed in all four species of humans, chimpanzees, rats, and mice by up to 6-fold. Taken together, the protein network database analysis suggests that reduced GLP-1R in the aged human brain is associated with glucose dysmetabolism, ferroptosis, and reduced DCX+ neurons, that may contribute to AD.<\/jats:p>","DOI":"10.3389\/fnagi.2024.1350239","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T20:41:29Z","timestamp":1718224889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Reduced GLP-1R availability in the caudate nucleus with Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Emma","family":"Barrett","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle","family":"Ivey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Coffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyera","family":"Pemberton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prabir","family":"Patra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James B.","family":"Day","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H. 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