Insulin Resistance and Alzheimers Disease Pathogenesis: Potential Mechanisms and Implications for Treatment
Abstract
Insulin modulates cognition and other aspects of normal brain function. Insulin resistance is characterized by chronic peripheral insulin elevations, and it is accompanied by reduced brain insulin levels and insulin activity. Obesity, type 2 diabetes mellitus and hypertension are strongly associated with insulin resistance. In addition, insulin resistance increases the risk of age-related memory impairment and Alzheimer's disease. Possible mechanisms through which these risks are increased include the effects of peripheral hyperinsulinemia on memory, CNS inflammation, and regulation of the beta-amyloid peptide. We have shown that raising plasma insulin in humans to levels that characterize patients with insulin resistance increases the levels of Abeta and inflammatory agents in brain. These convergent effects may impair memory and induce AD pathology. Therapeutic strategies focused on preventing or correcting insulin abnormalities may thus benefit a subset of adults with age-related memory impairment and AD.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Peripheral insulin resistance and hyperinsulinemia may also affect Alzheimer's disease directly.
“However, peripheral insulin resistance and hyperinsulinemia may also affect AD directly [22].”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [22]
Basic and experimental data show that diabetes and insulin resistance may affect amyloid clearance in the brain.
“This is supported by basic and experimental data showing that diabetes and insulin resistance may affect amyloid clearance in the brain [22].”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [22]
An elevated risk for AD exists in type 2 diabetes patients, who manifest deficient CNS insulin signaling.
“An elevated risk for AD also exists in type 2 diabetes patients, who manifest deficient CNS insulin signaling.”
From Protection of synapses against Alzheimer's-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomers (2009) · cites this paper as [31]
Cites
Insulin and neurodegenerative disease: shared and specific mechanisms
Craft, S., & Stennis Watson, G. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00681-7 · Cited by 830 · see citing works
Self-citationReger, M. A., Watson, G. S., Frey, W. H., Baker, L. D., Cholerton, B., Keeling, M. L., Belongia, D., Fishel, M. A., Plymate, S. R., Schellenberg, G. D., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.016 · Cited by 621 · see citing works
Self-citationIntracerebroventricular insulin enhances memory in a passive-avoidance task
Park, C. R., Seeley, R. J., Craft, S., & WOODS, S. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00220-6 · Cited by 343 · see citing works
Self-citationThe Role of Insulin in Human Brain Glucose Metabolism
Bingham, E., Hopkins, D., Smith, D., Pernet, A., Hallett, W. A., Reed, L. J., Marsden, P. K., & Amiel, S. A. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3384 · Cited by 293 · see citing works
Craft, S., Asthana, S., Cook, D. G., Baker, L. D., Cherrier, M. M., Purganan, K., Wait, C., Petrova, A., Latendresse, S. J., Watson, G. S., et al. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00087-2 · Cited by 255 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Epidemiology of Alzheimer disease
Reitz, C., Brayne, C., & Mayeux, R. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.2 · Cited by 1,675 · see citing works
Kalaria, R. N., Maestre, G. E., Arizaga, R., Friedland, R. P., Galasko, D., Hall, K., Luchsinger, J. A., Ogunniyi, A., Perry, E. K., Potocnik, F., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70169-8 · Cited by 1,233 · see citing works
Alzheimer’s disease is type 3 diabetes—Evidence reviewed
de la Monte, S. M., & Wands, J. R. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200619 · Cited by 1,158 · see citing works
McClean, P. L., Parthsarathy, V., Faivre, E., & Hölscher, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0529-11.2011 · Cited by 698 · see citing works
De Felice, F. G., Vieira, M. N. N., Bomfim, T. R., Decker, H., Velasco, P. T., Lambert, M. P., Viola, K. L., Zhao, W.-Q., Ferreira, S. T., & Klein, W. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809158106 · Cited by 657 · see citing works
Henderson, S. T., Vogel, J. L., Barr, L. J., Garvin, F., Jones, J. J., & Costantini, L. C. (2009) · Nutrition & Metabolism · doi:10.1186/1743-7075-6-31 · Cited by 548 · see citing works
Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway
Gabbouj, S., Ryhänen, S., Marttinen, M., Wittrahm, R., Takalo, M., Kemppainen, S., Martiskainen, H., Tanila, H., Haapasalo, A., Hiltunen, M., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00629 · Cited by 401 · see citing works
Insulin resistance and Alzheimer's disease
De La Monte, S. M. (2009) · BMB Reports · doi:10.5483/bmbrep.2009.42.8.475 · Cited by 392 · see citing works
Gold, M., Alderton, C., Zvartau-Hind, M., Egginton, S., Saunders, A. M., Irizarry, M., Craft, S., Landreth, G., Linnamägi, Ü., & Sawchak, S. (2010) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000318845 · Cited by 361 · see citing works
Self-citationDiabetes mellitus and Alzheimer's disease: shared pathology and treatment?
Akter, K., Lanza, E. A., Martin, S. A., Myronyuk, N., Rua, M., & Raffa, R. B. (2011) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2010.03830.x · Cited by 352 · see citing works
Ou, Z., Deng, L., Lu, Z., Wu, F., Liu, W., Huang, D., & Peng, Y. (2020) · Nutrition & Diabetes · doi:10.1038/s41387-020-0115-8 · Cited by 328 · see citing works
Campbell, J. M., Stephenson, M. D., de Courten, B., Chapman, I., Bellman, S. M., & Aromataris, E. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180263 · Cited by 292 · see citing works
Luchsinger, J. A., Perez, T., Chang, H., Mehta, P., Steffener, J., Pradabhan, G., Ichise, M., Manly, J., Devanand, D. P., & Bagiella, E. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150493 · Cited by 285 · see citing works
“This is supported by basic and experimental data showing that diabetes and insulin resistance may affect amyloid clearance in the brain [22].”
Bosco, D., Fava, A., Plastino, M., Montalcini, T., & Pujia, A. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01318.x · Cited by 283 · see citing works
de la Monte, S. M. (2012) · Drugs · doi:10.2165/11597760-000000000-00000 · Cited by 265 · see citing works
The Metabolic Syndrome and Development of Cognitive Impairment Among Older Women
Yaffe, K., Weston, A. L., Blackwell, T., & Krueger, K. A. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.566 · Cited by 220 · see citing works
Hsu, T. M., Konanur, V. R., Taing, L., Usui, R., Kayser, B. D., Goran, M. I., & Kanoski, S. E. (2015) · Hippocampus · doi:10.1002/hipo.22368 · Cited by 217 · see citing works
Blalock, E. M., Buechel, H. M., Popovic, J., Geddes, J. W., & Landfield, P. W. (2011) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2011.06.007 · Cited by 211 · see citing works
Body mass index and magnetic resonance markers of brain integrity in adults
Gazdzinski, S., Kornak, J., Weiner, M. W., & Meyerhoff, D. J. (2008) · Annals of Neurology · doi:10.1002/ana.21377 · Cited by 191 · see citing works
Pipatpiboon, N., Pintana, H., Pratchayasakul, W., Chattipakorn, N., & Chattipakorn, S. C. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12088 · Cited by 183 · see citing works
Clinical development of curcumin in neurodegenerative disease
Hu, S., Maiti, P., Ma, Q., Zuo, X., Jones, M. R., Cole, G. M., & Frautschy, S. A. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1044981 · Cited by 179 · see citing works
McClean, P. L., & Hölscher, C. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.07.015 · Cited by 170 · see citing works
Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis
Cheng, C., Lin, C.-H., Tsai, Y.-W., Tsai, C.-J., Chou, P.-H., & Lan, T.-H. (2014) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glu073 · Cited by 167 · see citing works
Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism
Schulz, T. J., & Tseng, Y.-H. (2009) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2009.10.019 · Cited by 154 · see citing works
Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus
Moroz, N., Tong, M., Longato, L., Xu, H., & de la Monte, S. M. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15103 · Cited by 151 · see citing works
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114 · see citing works
Insulin signaling effects on memory and mood
Reagan, L. P. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.10.012 · Cited by 118 · see citing works
McIntyre, R. S., Soczynska, J. K., Woldeyohannes, H. O., Miranda, A., Vaccarino, A., MacQueen, G., Lewis, G. F., & Kennedy, S. H. (2012) · Bipolar Disorders · doi:10.1111/bdi.12006 · Cited by 104 · see citing works
Type 2 diabetes, related conditions, in relation and dementia: An opportunity for prevention?
Luchsinger, J. A. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091687 · Cited by 91 · see citing works
Zhao, R. R., O’Sullivan, A. J., & Fiatarone Singh, M. A. (2018) · European Review of Aging and Physical Activity · doi:10.1186/s11556-018-0190-1 · Cited by 88 · see citing works
Obesity, Insulin Resistance, and Alzheimer's Disease
Hildreth, K. L., Van Pelt, R. E., & Schwartz, R. S. (2012) · Obesity · doi:10.1038/oby.2012.19 · Cited by 86 · see citing works
The Role of GLP-1 in Neuronal Activity and Neurodegeneration
Hölscher, C. (2010) · Vitamins & Hormones · doi:10.1016/b978-0-12-381517-0.00013-8 · Cited by 74 · see citing works
Campos-Peña, V., Toral-Rios, D., Becerril-Pérez, F., Sánchez-Torres, C., Delgado-Namorado, Y., Torres-Ossorio, E., Franco-Bocanegra, D., & Carvajal, K. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6768 · Cited by 58 · see citing works
Lee, C. G., Schwartz, A. V., Yaffe, K., Hillier, T. A., LeBlanc, E. S., Cawthon, P. M., & the Study of Osteoporotic Fractures Research Group (2013) · Journal of the American Geriatrics Society · doi:10.1111/jgs.12502 · Cited by 53 · see citing works
Nutritional interventions for Alzheimer's prevention: a clinical precision medicine approach
Schelke, M. W., Hackett, K., Chen, J. L., Shih, C., Shum, J., Montgomery, M. E., Chiang, G. C., Berkowitz, C., Seifan, A., Krikorian, R., et al. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13070 · Cited by 51 · see citing works
Zolochevska, O., & Taglialatela, G. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160518142110 · Cited by 49 · see citing works
Therapies modulating insulin resistance in Parkinson’s disease: A cross talk
Sharma, T., Kaur, D., Grewal, A. K., & Singh, T. G. (2021) · Neuroscience Letters · doi:10.1016/j.neulet.2021.135754 · Cited by 44 · see citing works
Soeda, Y., Tsuneki, H., Muranaka, H., Mori, N., Hosoh, S., Ichihara, Y., Kagawa, S., Wang, X., Toyooka, N., Takamura, Y., et al. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0163 · Cited by 38 · see citing works
Ho, L., Yemul, S., Knable, L., Katsel, P., Zhao, R., Haroutunian, V., & Pasinetti, G. M. (2012) · International Journal of Alzheimer's Disease · doi:10.1155/2012/321280 · Cited by 21 · see citing works
Luchsinger, J. A. (2010) · Research and Perspectives in Alzheimer's Disease · doi:10.1007/978-3-642-04300-0_7 · Cited by 3 · see citing works
- Authors
- Craft, S.
- Affiliations
- University of Washington (US)
- Corresponding author
- Craft, Suzanne
- ORCID
- Craft, Suzanne
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2007-04-01
- Volume
- 4
- Issue
- 2
- Pages
- 147-152
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W1978769917
- Cited by
- 487
- References
- 5
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 9 · 2023: 15 · 2022: 14 · 2021: 15 · 2020: 27 · 2019: 23 · 2018: 21 · 2017: 32 · 2016: 33 · 2015: 27 · 2014: 38 · 2013: 33 · 2012: 41
- FWCI
- 21.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01-AG-10880, R01AG010880)
- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin resistance, Alzheimer's disease, hyperinsulinemia, brain insulin, amyloid-beta, neuroinflammation, age-related memory impairment, type 2 diabetes, obesity, hypertension, insulin therapy
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Insulin, Insulin Resistance, Models, Biological, Obesity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
