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- Title
Reduced GLP-1R availability in the caudate nucleus with Alzheimer's disease.
- Authors
Barrett, Emma; Ivey, Gabrielle; Cunningham, Adam; Coffman, Gary; Pemberton, Tyera; Chan Lee; Patra, Prabir; Day, James B.; Lee, Peter H. U.; Shim, Joon W.
- Abstract
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's 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.
- Subjects
GLUCOSE metabolism; GLUCAGON-like peptide-1 agonists; HYDROCEPHALUS; ALZHEIMER'S disease; RESEARCH funding; KRUSKAL-Wallis Test; FUNERAL industry; BASAL ganglia; REVERSE transcriptase polymerase chain reaction; MANN Whitney U Test; CHRONIC diseases; MICE; RATS; COGNITION disorders; ANIMAL experimentation; DATA analysis software; PRIMATES; NUCLEAR factor E2 related factor
- Publication
Frontiers in Aging Neuroscience, 2024, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2024.1350239