Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease
Open accessAbstract
Compelling evidence indicates that excess consumption of sugar-sweetened beverages plays an important role in the epidemic of obesity, a major risk factor for type 2 diabetes mellitus. Type 2 diabetes mellitus has been associated with a higher incidence of Alzheimer disease (AD). High fat diets promote AD-like pathology in mice. It is not known whether consumption of excess sugar as in calorically sweetened beverages with an otherwise normal diet affects the development of AD. In the present study, we provided 10% sucrose-sweetened water to a transgenic mouse model of AD with a normal rodent diet. Compared with the control mice with no sucrose added in the water, the sucrose group gained more body weight and developed glucose intolerance, hyperinsulinemia, and hypercholesterolemia. These metabolic changes were associated with the exacerbation of memory impairment and a 2-3-fold increase in insoluble amyloid-beta protein levels and deposition in the brain. We further showed that the levels of expression and secretase-cleaved products of amyloid-beta precursor protein were not affected by sucrose intake. The steady-state levels of insulin-degrading enzyme did not change significantly, whereas there was a 2.5-fold increase in brain apoE levels. Therefore, we concluded that the up-regulation of apoE accelerated the aggregation of Abeta, resulting in the exacerbation of cerebral amyloidosis in sucrose-treated mice. These data underscore the potential role of dietary sugar in the pathogenesis of AD and suggest that controlling the consumption of sugar-sweetened beverages may be an effective way to curtail the risk of developing AD.
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Experimentally-induced diabetes causes accelerated cognitive failure in AD mouse models.
“Experimentally-induced diabetes moreover causes accelerated cognitive failure in AD mouse models (Cao et al., 2007; Ho et al., 2004; Plaschke et al., 2010; Wang et al., 2010).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Cao et al., 2007
AD-like changes have been observed in experimental models of insulin resistance, including animals fed a high fat diet or receiving intracerebral or IP injections of streptozotocin.
“Supporting this idea, AD-like changes have been observed in experimental models of insulin resistance, including animals fed a high fat diet or receiving intracerebral or IP injections of streptozotocin (Cao et al., 2007; Labak et al., 2010; Lester-Coll et al., 2006; Ma et al., 2009; Pratchayasakul et al., 2011; Tong et al., 2009; Zhang et al., 2009).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Cao et al., 2007
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- Authors
- Cao, D., Lu, H., Lewis, T. L., & Li, L.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Li, Ling
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 282
- Issue
- 50
- Pages
- 36275-36282
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2008337884
- Cited by
- 336
- References
- 42
- Citations by year
- 2026: 1 · 2025: 16 · 2024: 8 · 2023: 11 · 2022: 17 · 2021: 18 · 2020: 18 · 2019: 21 · 2018: 18 · 2017: 24 · 2016: 26 · 2015: 25 · 2014: 20 · 2013: 30 · 2012: 22
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- National Institutes of Health
- National Institute on Aging (R21AG025949, AG025949)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- sugar-sweetened beverages, Alzheimer's disease, insulin resistance, memory impairment, cerebral amyloidosis, amyloid-beta aggregation, apolipoprotein E, insulin-degrading enzyme, hypercholesterolemia, impaired glucose tolerance, hyperinsulinemia, type 2 diabetes, transgenic mouse model, dietary sugar
- MeSH terms
- Alzheimer Disease, Amyloidosis, Animals, Apolipoproteins E, Beverages, Brain, Diabetes Mellitus, Type 2, Disease Models, Animal, Humans, Hypercholesterolemia, Insulin Resistance, Mice, Transgenic, Obesity, Risk Factors, Sucrose, Sweetening Agents, Water, Amyloid beta-Peptides, Glucose Intolerance, Mice, Amyloid Precursor Protein Secretases
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