{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:42:57Z","timestamp":1774460577290,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007660","name":"University of Antwerp","doi-asserted-by":"publisher","award":["33931"],"award-info":[{"award-number":["33931"]}],"id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer\u2019s disease (AD). As insulin resistance can be caused by high-stress hormone levels and since hypercortisolism appears to be an important risk factor of AD, we aimed to investigate the systemic insulin functionality and circulating stress hormone levels in a mutant humanized amyloid precursor protein (APP) overexpressing (hAPP23+\/\u2212) AD mouse model. Memory and spatial learning of male hAPP23+\/\u2212 and C57BL\/6 (wild type, WT) mice were assessed by a Morris Water Maze (MWM) test at the age of 4 and 12 months. The systemic metabolism was examined by intraperitoneal glucose and insulin tolerance tests (GTT, ITT). Insulin and corticosterone levels were determined in serum. In the hippocampus, parietal and occipital cortex of hAPP23+\/\u2212 brains, amyloid-beta (A\u03b2) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+\/\u2212 mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+\/\u2212 animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+\/\u2212 mice exhibited peripheral insulin resistance compared to WT mice at 4 months, which stabilized at 12 months of age. Serum insulin levels were similar between genotypes at 4 months of age but were significantly higher in hAPP23+\/\u2212 mice at 12 months of age. Peripheral glucose homeostasis remained unchanged. These results indicate that peripheral insulin resistance combined with elevated circulating stress hormone levels could be potential biomarkers of the pre-symptomatic phase of AD.<\/jats:p>","DOI":"10.3390\/ijms22136656","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:02:10Z","timestamp":1624366930000},"page":"6656","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"22","author":[{"given":"Jhana O.","family":"Hendrickx","sequence":"first","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie","family":"De Moudt","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Calus","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1967-9343","authenticated-orcid":false,"given":"Wim","family":"Martinet","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8640-6620","authenticated-orcid":false,"given":"Pieter-Jan D. F.","family":"Guns","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1397-1810","authenticated-orcid":false,"given":"Lynn","family":"Roth","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter P.","family":"De Deyn","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"},{"name":"Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen, 9727 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debby","family":"Van Dam","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"},{"name":"Department of Neurology and Alzheimer Center, University of Groningen and University Medical Center Groningen, 9727 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3848-8702","authenticated-orcid":false,"given":"Guido R. Y.","family":"De Meyer","sequence":"additional","affiliation":[{"name":"Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1007\/s00259-020-04969-7","article-title":"Clinical impact of 18 F-FDG-PET among memory clinic patients with uncertain diagnosis","volume":"48","author":"Perini","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yamanakkanavar, N., Choi, J.Y., and Lee, B. (2020). MRI segmentation and classification of human brain using deep learning for diagnosis of alzheimer\u2019s disease: A survey. 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