Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease
Abstract
The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.
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Brain insulin signaling declines with age, and this is the primary risk factor for Alzheimer's disease.
“Brain insulin signaling declines with age (Frolich et al., 1998; , 1999; Hoyer, 1998; Rivera et al., 2005), the primary risk factor for AD.”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Frolich et al., 1998
Levels of brain insulin and insulin receptors are lower in Alzheimer's disease.
“levels of brain insulin and insulin receptors (IRs) are lower in AD (Frolich et al., 1998; Rivera et al., 2005).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Frolich et al., 1998
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- Authors
- Frölich, L., Blum-Degen, D., Bernstein, H.-G., Engelsberger, S., Humrich, J., Laufer, S., Muschner, D., Thalheimer, A., Türk, A., Hoyer, S., Zöchling, R., Boissl, K. W., Jellinger, K., & Riederer, P.
- Affiliations
- Goethe University Frankfurt (DE)
- University of Würzburg (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Heidelberg University (DE)
- Ludwig Boltzmann für Klinische Neurobiologie (AT)
- Venue
- Journal of Neural Transmission
- Published
- 1998
- Volume
- 105
- Issue
- 4
- Pages
- 423
- ISSN
- 0300-9564 (ISSN-L)
- OpenAlex
- W2087443596
- Cited by
- 748
- References
- 61
- Citations by year
- 2026: 7 · 2025: 22 · 2024: 15 · 2023: 24 · 2022: 35 · 2021: 39 · 2020: 36 · 2019: 49 · 2018: 39 · 2017: 26 · 2016: 27 · 2015: 38 · 2014: 31 · 2013: 36 · 2012: 41
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Neural Transmission (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Julius-Maximilians-Universität Würzburg
- 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 › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- sporadic Alzheimer's disease, brain insulin, insulin receptor, C-peptide, insulin-like growth factor I, IGF-1 receptor, tyrosine kinase activity, insulin signaling, brain aging, insulin immunoreactivity, pyramidal neurons, glucose metabolism
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, C-Peptide, Frontal Lobe, Humans, Insulin, Middle Aged, Neurons, Occipital Lobe, Parietal Lobe, Receptor, Insulin, Reference Values, Temporal Lobe
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