Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: Relationship to severity of dementia and apolipoprotein E genotype
Abstract
Patients with Alzheimer's disease (AD) have elevations of fasting plasma insulin that are hypothesized to be associated with disrupted brain insulin metabolism. We examined paired fasted plasma and CSF insulin levels in 25 patients with AD and 14 healthy age-matched adults and determined whether insulin levels were related to severity of dementia and apolipoprotein E-epsilon4 homozygosity, a known genetic risk factor for AD. The AD patients had lower CSF insulin, higher plasma insulin, and a reduced CSF-to-plasma insulin ratio when compared with healthy adults. The differences were greater for patients with more advanced AD. Patients who were not apolipoprotein E-epsilon4 homozygotes had higher plasma insulin levels and reduced CSF-to-plasma ratios, whereas epsilon4 homozygotes with AD had normal values. Both plasma and CSF insulin levels are abnormal in AD, and there are metabolic differences among apolipoprotein E genotypes.
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There is a potential link between AD and insulin resistance, with decreased key insulin signaling proteins and increased insulin resistance markers in the brains of AD mice.
“Recent studies have suggested a potential link between AD and insulin resistance, which exhibits a decreased level of key insulin signaling proteins and an increased level of insulin resistance markers in the brains of AD mice (Craft et al., 1998; Arnold et al., 2018; Kshirsagar et al., 2021).”
From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as Craft et al., 1998
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- Authors
- Craft, S., Peskind, E., Schwartz, M. W., Schellenberg, G. D., Raskind, M., & Porte, D.
- Affiliations
- University of Washington (US)
- Venue
- Neurology
- Published
- 1998-01
- Volume
- 50
- Issue
- 1
- Pages
- 164-168
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2047509507
- Cited by
- 560
- References
- 0
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 15 · 2023: 15 · 2022: 28 · 2021: 29 · 2020: 18 · 2019: 24 · 2018: 20 · 2017: 29 · 2016: 19 · 2015: 23 · 2014: 31 · 2013: 24 · 2012: 27
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG08419, AG 05136, AG10880, R01AG008419, P50AG005136)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid insulin, plasma insulin, APOE ε4, dementia severity, fasting insulin
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Homozygote, Humans, Insulin, Middle Aged, Apolipoprotein E4
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