Cited by 392Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Insulin resistance and Alzheimer's disease

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De La Monte, Suzanne M.·2009·BMB Reports

DOI 10.5483/bmbrep.2009.42.8.475PMC PMC4600067

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Abstract

Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer's disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production.

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Authors: De La Monte, S. M.
Venue: BMB Reports
Publisher: Korean Society for Biochemistry and Molecular Biology - BMB Reports
Published: 2009-08-31
Volume: 42
Issue: 8
Pages: 475-481
ISSN: 1976-6696 (ISSN-L)
DOI: 10.5483/bmbrep.2009.42.8.475
PMC: PMC4600067
OpenAlex: W1963640549
Cited by: 392
References: 57
Citations by year: 2026: 7 · 2025: 11 · 2024: 17 · 2023: 23 · 2022: 29 · 2021: 22 · 2020: 22 · 2019: 21 · 2018: 20 · 2017: 24 · 2016: 25 · 2015: 36 · 2014: 24 · 2013: 23 · 2012: 39
FWCI: 3.22
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
Locations: BMB Reports (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5r01aa011431-26)
National Institute on Alcohol Abuse and Alcoholism (R01-AA011431, AA-12908, K24AA016126, AA-16126, AA11431, R56AA011431, R01AA012908, R37AA011431)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: brain insulin resistance, Alzheimer's disease, insulin-like growth factor, cognitive impairment, neurodegeneration, type 2 diabetes, obesity, liver-brain axis, ceramide, blood-brain barrier, oxidative stress, neuroinflammation, neuronal cell death, insulin signaling
MeSH terms: Alzheimer Disease, Animals, Brain, Humans, Insulin Resistance, Models, Biological, Somatomedins, Amyloid beta-Protein Precursor

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