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Low density of sigma1 receptors in early Alzheimer’s disease
Open accessAbstract
Objective The sigma(1) receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma(1) receptors were reduced in the hippocampus in Alzheimer's disease (AD). However, in vivo imaging of sigma(1) receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma(1) receptors in AD using [(11)C]SA4503 positron emission tomography (PET).Methods We studied five AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [(11)C]SA4503. A two-tissue three-compartment model was used to estimate K (1), k (2), k (3), k (4), and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k (3) to k (4) was computed as the binding potential (BP), which is linearly related to the density of sigma(1) receptors. Unpaired t tests were used to compare K (1) and BP in patients with AD and normal subjects.Results As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K (1) was significantly lower in the parietal lobe.Conclusions [(11)C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma(1) receptors is reduced in early AD.
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“Instead, in the very early phases of AD, a significant loss of σ1R occurs in the brain [115,116].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [115]
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Cited by
Sorted by citations
The pharmacology of sigma-1 receptors.
Maurice, T., & Su, T.-P. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.07.001 · Cited by 654
“It is worth mentioning that in a human positron emission tomography (PET) study employing [11C]SA4503, a lower density of sigma-1 receptors was found in early Alzheimer's patients compared to age-matched controls (Mishina et al., 2008).”
ResultHedskog, L., Pinho, C. M., Filadi, R., Rönnbäck, A., Hertwig, L., Wiehager, B., Larssen, P., Gellhaar, S., Sandebring, A., Westerlund, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300677110 · Cited by 478
“In concordance, decreased levels of σ1R have been detected postmortem in the hippocampus (37) and in living patients already at an early AD disease stage using imaging techniques (38).”
BackgroundIzzo, N. J., Xu, J., Zeng, C., Kirk, M. J., Mozzoni, K., Silky, C., Rehak, C., Yurko, R., Look, G., Rishton, G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111899 · Cited by 157
“In severely demented Alzheimer’s disease patients (CDR stage 3) expected to have a high degree of cell loss, the density of sigma-2 receptors remains unchanged compared to age-matched normal individuals, while the density of the unrelated sigma-1 receptor is decreased by 54%, as has been previously reported [43].”
The sigma-1 receptor: roles in neuronal plasticity and disease
Kourrich, S., Su, T.-P., Fujimoto, M., & Bonci, A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.09.007 · Cited by 245
Role of sigma-1 receptors in neurodegenerative diseases
Nguyen, L., Lucke-Wold, B. P., Mookerjee, S. A., Cavendish, J. Z., Robson, M. J., Scandinaro, A. L., & Matsumoto, R. R. (2014) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2014.12.005 · Cited by 236
Metadata
- Authors
- Mishina, M., Ohyama, M., Ishii, K., Kitamura, S., Kimura, Y., Oda, K.-I., Kawamura, K., Sasaki, T., Kobayashi, S., Katayama, Y., & Ishiwata, K.
- Affiliations
- Tokyo Metropolitan Institute of Gerontology (JP)
- Nippon Medical School Musashi Kosugi Hospital (JP)
- Chiba Hokusou Hospital (JP)
- Nippon Medical School (JP)
- Corresponding author
- Mishina, Masahiro
- ORCID
- Venue
- Annals of Nuclear Medicine
- Published
- 2008-04
- Volume
- 22
- Issue
- 3
- Pages
- 151-156
- ISSN
- 0914-7187 (ISSN-L)
- 1864-6433
- OpenAlex
- W2169525045
- Cited by
- 172
- References
- 45
- Citations by year
- 2026: 9 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 14 · 2019: 7 · 2018: 4 · 2017: 14 · 2016: 8 · 2015: 10 · 2014: 20 · 2013: 12 · 2012: 7
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- green
- repo.qst.go.jp
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Annals of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- QST-Repository (National Institutes for Quantum and Radiological Science and Technology) (submittedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Receptor Mechanisms and Effects
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- sigma-1 receptor, Alzheimer's disease, early Alzheimer's disease, receptor binding potential, receptor density
- MeSH terms
- Aged, Alzheimer Disease, Brain Chemistry, Carbon Radioisotopes, Cerebellum, Cerebral Cortex, Female, Humans, Male, Piperazines, Thalamus, Tissue Distribution, Receptors, sigma, Radiopharmaceuticals, Positron-Emission Tomography
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