D1-dopamine receptor abnormality in frontal cortex points to a functional alteration of cortical cell membranes in Alzheimer’s disease
Abstract
D1-dopamine receptors and their high-agonist affinity (RH) sites were determined in postmortem-obtained frontal cortex from seven patients with histopathologically confirmed Alzheimer's disease and from seven controls matched for sex, age, and postmortem delay. Total D1-dopamine receptor concentration was unchanged in patients with Alzheimer's disease compared with controls, but the RH sites were significantly reduced in number. Since the RH sites are thought to represent a conformational change of the receptors, induced by the interaction of agonist-bound receptor with a signal transduction protein located in the cell membrane, the reduced ratio of RH sites to total receptors suggests a functional alteration of cortical cell membranes in Alzheimer's disease. Such a cell membrane abnormality might explain why substitution therapy in Alzheimer's disease has been largely disappointing.
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Dopaminergic neurotransmission, centrally implicated in the brain reward system and known to decline with aging, plays important roles in non-pharmacological strategies aimed to improve age-related cognitive decline, such as environmental enrichment and physical exercise.
“dopaminergic neurotransmission, centrally implicated in the brain reward system and known to decline with aging (De Keyser et al., 1990), plays important roles in non-pharmacological strategies aimed to improve age-related cognitive decline, such as environmental enrichment and physical exercise (van Praag et al., 2000).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as De Keyser et al., 1990
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The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
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- Authors
- De Keyser, J., Ebinger, G., & Vauquelin, G.
- ORCID
- Vauquelin, G.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 1990-07-01
- Volume
- 47
- Issue
- 7
- Pages
- 761-763
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2094701828
- Cited by
- 49
- References
- 19
- Citations by year
- 2019: 1 · 2018: 1 · 2016: 1 · 2014: 1 · 2013: 1
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- dopamine D1 receptor, Alzheimer's disease, frontal cortex, receptor conformational change, receptor agonist binding, replacement therapy, postmortem brain
- MeSH terms
- Aged, Alzheimer Disease, Cell Membrane, Female, Frontal Lobe, Humans, Male, Middle Aged, Receptors, Dopamine
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