Reduced Glucose Transporter at the Blood‐Brain Barrier and in Cerebral Cortex in Alzheimer Disease
Abstract
We studied the hexose transporter protein of the frontal and temporal neocortex, hippocampus, putamen, cerebellum, and cerebral microvessels (which constitute the blood-brain barrier) in Alzheimer disease and control subjects by reversible and covalent binding with [3H]cytochalasin B and by immunological reactivity. In Alzheimer disease subjects, we found a marked decrease in the hexose transporter in brain microvessels and in the cerebral neocortex and hippocampus, regions that are most affected in Alzheimer disease, but there were no abnormalities in the putamen or cerebellum. Hexose transporter reduction in cerebral microvessels of Alzheimer subjects is relatively specific because other enzyme markers of brain endothelium were not significantly altered. The low density of the hexose transporter at the blood-brain barrier and in the cerebral cortex in Alzheimer disease may be related to decreased in vivo measurements of cerebral oxidative metabolism.
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AD post mortem studies show diminished expression of GLUT1 in brain capillaries.
“This is consistent with AD post mortem studies showing diminished expression of GLUT1 in brain capillaries (261, 301, 422, 541).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [301]
In Alzheimer's disease, endothelial-specific GLUT1 transporter levels at the blood-brain barrier are greatly reduced.
“The levels of endothelial-specific GLUT1 transporter at the BBB are greatly reduced in AD (261, 301, 422, 541).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [301]
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Initiative, O. B. O. A. D. N., Ou, Y.-N., Xu, W., Li, J.-Q., Guo, Y., Cui, M., Chen, K.-L., Huang, Y.-Y., Dong, Q., Tan, L., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0512-1 · Cited by 155 · see citing works
Pereira, C., Santos, M. S., & Oliveira, C. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0241 · Cited by 156 · see citing works
Pan, Y., & Nicolazzo, J. A. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.04.009 · Cited by 131 · see citing works
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Ott, B. R., Jones, R. N., Daiello, L. A., de la Monte, S. M., Stopa, E. G., Johanson, C. E., Denby, C., & Grammas, P. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00245 · Cited by 91 · see citing works
Xu, J., Begley, P., Church, S. J., Patassini, S., McHarg, S., Kureishy, N., Hollywood, K. A., Waldvogel, H. J., Liu, H., Zhang, S., et al. (2016) · Scientific Reports · doi:10.1038/srep27524 · Cited by 85 · see citing works
- Authors
- Kalaria, R. N., & Harik, S. I.
- Affiliations
- University Hospitals of Cleveland (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1989-10
- Volume
- 53
- Issue
- 4
- Pages
- 1083-1088
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2028384515
- Cited by
- 338
- References
- 0
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 11 · 2023: 12 · 2022: 8 · 2021: 17 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 7 · 2016: 15 · 2015: 12 · 2014: 7 · 2013: 7 · 2012: 10
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-08012)
- National Heart, Lung, and Blood Institute (HL-35617)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- glucose transporters, Alzheimer's disease, blood-brain barrier, cerebral cortex, hippocampus, cerebral microvasculature, hexose transporters, cytochalasin B binding, brain endothelium, cerebral oxidative metabolism, frontal cortex, temporal cortex
- MeSH terms
- Adult, Aged, Aging, Alzheimer Disease, Blood-Brain Barrier, Cerebral Cortex, Cerebrovascular Circulation, Cytochalasin B, Female, Humans, Kinetics, Male, Microcirculation, Monosaccharide Transport Proteins, Reference Values
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