Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease
Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s 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 syst...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/13/6656 |
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| author | Jhana O. Hendrickx Sofie De Moudt Elke Calus Wim Martinet Pieter-Jan D. F. Guns Lynn Roth Peter P. De Deyn Debby Van Dam Guido R. Y. De Meyer |
| author_facet | Jhana O. Hendrickx Sofie De Moudt Elke Calus Wim Martinet Pieter-Jan D. F. Guns Lynn Roth Peter P. De Deyn Debby Van Dam Guido R. Y. De Meyer |
| author_sort | Jhana O. Hendrickx |
| collection | DOAJ |
| description | Increasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s 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+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− 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+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− 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+/− 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. |
| first_indexed | 2024-03-10T10:11:23Z |
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| language | English |
| last_indexed | 2024-03-10T10:11:23Z |
| publishDate | 2021-06-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1d85c304985641a5b8dc26727b5e13142023-11-22T01:09:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213665610.3390/ijms22136656Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s DiseaseJhana O. Hendrickx0Sofie De Moudt1Elke Calus2Wim Martinet3Pieter-Jan D. F. Guns4Lynn Roth5Peter P. De Deyn6Debby Van Dam7Guido R. Y. De Meyer8Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumLaboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, Campus Drie Eiken, Universiteitsplein 1, University of Antwerp, 2610 Wilrijk, Antwerp, BelgiumIncreasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer’s 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+/−) AD mouse model. Memory and spatial learning of male hAPP23+/− 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+/− brains, amyloid-beta (Aβ) deposits were present at 12 months of age. MWM demonstrated a cognitive decline in hAPP23+/− mice at 12 but not at 4 months, evidenced by increasing total path lengths and deteriorating probe trials compared to WT mice. hAPP23+/− animals presented increased serum corticosterone levels compared to WT mice at both 4 and 12 months. hAPP23+/− 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+/− 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.https://www.mdpi.com/1422-0067/22/13/6656hypercortisolisminsulin resistancehypermetabolismcognitive declineAlzheimer’s disease |
| spellingShingle | Jhana O. Hendrickx Sofie De Moudt Elke Calus Wim Martinet Pieter-Jan D. F. Guns Lynn Roth Peter P. De Deyn Debby Van Dam Guido R. Y. De Meyer Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease International Journal of Molecular Sciences hypercortisolism insulin resistance hypermetabolism cognitive decline Alzheimer’s disease |
| title | Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease |
| title_full | Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease |
| title_fullStr | Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease |
| title_full_unstemmed | Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease |
| title_short | Serum Corticosterone and Insulin Resistance as Early Biomarkers in the hAPP23 Overexpressing Mouse Model of Alzheimer’s Disease |
| title_sort | serum corticosterone and insulin resistance as early biomarkers in the happ23 overexpressing mouse model of alzheimer s disease |
| topic | hypercortisolism insulin resistance hypermetabolism cognitive decline Alzheimer’s disease |
| url | https://www.mdpi.com/1422-0067/22/13/6656 |
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