Loss of Dopamine Uptake Sites Labeled with [ 3 H]GBR-12935 in Alzheimer’s Disease
Abstract
The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30-40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR-12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites.
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Multiple studies have established an early link between AD and deficits in mesocorticolimbic DA signalling.
“multiple studies established an early link be tween AD and deficits in mesocorticolimbic DA signalling”
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Laruelle, M., Baldwin, R. M., Malison, R. T., Zea‐Ponce, Y., Zoghbi, S. S., Al‐Tikeriti, M. S., Sybirska, E. H., Zimmermann, R. C., Wisniewski, G., Neumeyer, J. L., et al. (1993) · Synapse · doi:10.1002/syn.890130402 · Cited by 351 · see citing works
Westlake, T. M., Howlett, A., Bonner, T., Matsuda, L., & Herkenham, M. (1994) · Neuroscience · doi:10.1016/0306-4522(94)90511-8 · Cited by 290 · see citing works
“Is dopamine involved in Alzheimer's disease?”
Martorana, A., & Koch, G. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00252 · Cited by 276 · see citing works
“, and Halliday, G. (2013). Can we clinically diagnose dementia with Lewy bodies yet? Transl. Neurodegener. 2, 4. doi: 10.1186/2047-9158-2-4 Iqbal, K., Alonso, A. D., Gondal, J. A., Gong, C. X., Haque, N., Khatoon, S., et al. (2000). Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach.”
BackgroundInfluentialRegulation of brain function by exercise
Sutoo, D., & Akiyama, K. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00030-5 · Cited by 275 · see citing works
Pan, X., Kaminga, A. C., Wen, S. W., Wu, X., Acheampong, K., & Liu, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00175 · Cited by 269 · see citing works
Trillo, L., Das, D., Hsieh, W., Medina, B., Moghadam, S., Lin, B., Dang, V., Sanchez, M. M., Miguel, Z. D., Ashford, J. W., et al. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.05.008 · Cited by 224 · see citing works
Monoaminergic neurotransmitters, their precursors and metabolites in brains of Alzheimer patients
Štorga-Tomić, D., Vrečko, K., Birkmayer, J. G. D., & Reibnegger, G. J. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(95)12256-7 · Cited by 209 · see citing works
Br�cke, T., Kornhuber, J., Angelberger, P., Asenbaum, S., Frassine, H., & Podreka, I. (1993) · Journal of Neural Transmission · doi:10.1007/bf01245007 · Cited by 199 · see citing works
[ 99m Tc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent
Kung, M., Stevenson, D. A., Pl�ssl, K., Meegalla, S. K., Beckwith, A. W., Essman, W. D., Mu, M., Lucki, I., & Kung, H. F. (1997) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/bf00881808 · Cited by 162 · see citing works
“A significant reduction in the density of these transporters has been reported in postmortem examination of the basal ganglia region of brains from patients with Parkinson's and Alzheimer's diseases [3-5].”
BackgroundThe Role of Dopamine in Symptoms and Treatment of Apathy in Alzheimer's Disease
Mitchell, R., Herrmann, N., & Lanctôt, K. (2011) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00161.x · Cited by 141 · see citing works
“Another study used a different uptake ligand—[(3)H]GBR-12935—to assay DA uptake and found a 50% reduced uptake in the putamen (a structure within the striatum) of AD patients [67].”
Murray, A. M., Weihmueller, F. B., Marshall, J. F., Hurtig, H. I., Gottleib, G. L., & Joyce, J. N. (1995) · Annals of Neurology · doi:10.1002/ana.410370306 · Cited by 135 · see citing works
Pharmacological interventions for apathy in Alzheimer's disease
Ruthirakuhan, M. T., Herrmann, N., Abraham, E. H., Chan, S., & Lanctôt, K. L. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012197.pub2 · Cited by 113 · see citing works
Neurochemical aspects on aging and diseases with cognitive impairment
Gottfries, C. G. (1990) · Journal of Neuroscience Research · doi:10.1002/jnr.490270415 · Cited by 107 · see citing works
“In basal ganglia, both DA and HVA are significantly reduced in AD/SDAT patients (for a review, see Mann et a]., 1987; Gottfries, 1988; Cowburn et al., 1989; Allard et al., 1990).”
BackgroundSelf-citationLa Barbera, L., Vedele, F., Nobili, A., Krashia, P., Spoleti, E., Latagliata, E. C., Cutuli, D., Cauzzi, E., Marino, R., Viscomi, M. T., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102031 · Cited by 98 · see citing works
Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters
Attali, G., Weizman, A., Gil‐Ad, I., & Rehavi, M. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00136-4 · Cited by 95 · see citing works
Gottfries, C., Karlsson, I., & Svennerholm, L. (1996) · International Psychogeriatrics · doi:10.1017/s1041610296002736 · Cited by 85 · see citing works
Self-citationRomero, J., Berrendero, F., Garcı́a-Gil, L., de la Cruz, P., Ramos, J. A., & Fernández‐Ruíz, J. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00552-6 · Cited by 86 · see citing works
IPT: A novel iodinated ligand for the CNS dopamine transporter
Kung, M., Essman, W. D., Frederick, D., Meegalla, S. K., Goodman, M. M., Mu, M., Lucki, I., & Kung, H. F. (1995) · Synapse · doi:10.1002/syn.890200405 · Cited by 72 · see citing works
Inhibiting BACE1 to reverse synaptic dysfunctions in Alzheimer’s disease
Yan, R., Fan, Q., Zhou, J., & Vassar, R. J. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.025 · Cited by 71 · see citing works
“…due to dramatically reduced expressions of both D1R and D2R, as well as DAT and TH, are found mainly in prefrontal cortex and hippocampus (Allard et al., 1990; Cross et al., 1984; Joyce et al., 1998; Kemppainen et al., 2003; Kumar and Patel, 2007; Murray et al., 1995; Rinne et al.,…”
PET shows that striatal dopamine D1 and D2 receptors are differentially affected in AD
Kemppainen, N. M., Ruottinen, H., Någren, K., & Rinne, J. O. (2000) · Neurology · doi:10.1212/wnl.55.2.205 · Cited by 70 · see citing works
Imaging of serotonin and dopamine transporters in the living human brain
Kuikka, J. T., Tiihonen, J., Bergstr�m, K. A., Karhu, J., Hartikainen, P., Viinam�ki, H., L�nsimies, E., Lehtonen, J., & Hakola, P. (1995) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/bf00941852 · Cited by 70 · see citing works
“Kuikka ease [2] in post-mortem studies.”
Monoaminergic System Modulation in Depression and Alzheimer’s Disease: A New Standpoint?
Morgese, M. G., & Trabace, L. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00483 · Cited by 69 · see citing works
Sensitivity to ageing of the limbic dopaminergic system: a review
Barili, P., Carolis, G. D., Zaccheo, D., & Amenta, F. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00104-3 · Cited by 64 · see citing works
Significance of decreased lumbar CSF levels of HVA and 5-HIAA in Alzheimer's disease
Blennow, K., Wallin, A., Gottfries, C. G., et al. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90017-r · Cited by 60 · see citing works
Self-citationCatecholamines in Alzheimer's Disease: A Systematic Review and Meta-Analysis
Pan, X., Kaminga, A. C., Jia, P., Wen, S. W., Acheampong, K., & Liu, A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00184 · Cited by 44 · see citing works
Iaccarino, L., Sala, A., Caminiti, S. P., Presotto, L., Perani, D., & Initiative, F. T. A. D. N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-190954 · Cited by 40 · see citing works
Dopamine uptake sites in Parkinson's disease and in dementia of the Alzheimer type
Allard, P. O., Rinne, J. O., & Marcusson, J. O. (1994) · Brain Research · doi:10.1016/0006-8993(94)91242-4 · Cited by 40 · see citing works
Self-citationThe VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer's disease
Krashia, P., Spoleti, E., & D’Amelio, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1039725 · Cited by 39 · see citing works
The neurochemistry of Alzheimer type, vascular type and mixed type dementias compared
Gsell, W., Strein, I., & Riederer, P. F. (1996) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6892-9_5 · Cited by 37 · see citing works
Odano, I., Varrone, A., Savić, I., Ciumas, C., Karlsson, P., Jučaitė, A., Halldin, C., & Farde, L. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.10.067 · Cited by 36 · see citing works
Spoleti, E., Krashia, P., Barbera, L. L., Nobili, A., Lupaşcu, C. A., Giacalone, E., Keller, F., Migliore, M., Renzi, M., & D’Amelio, M. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113969 · Cited by 28 · see citing works
Mizukawa, K., McGeer, E. G., & McGeer, P. L. (1993) · Molecular and Chemical Neuropathology · doi:10.1007/bf03160027 · Cited by 24 · see citing works
“Allard et al. (1990) previously reported a high correlation between the [ 3H]GBR-12935 binding and DA levels in individual control putamen samples.”
BackgroundDevelopmental and age-related alterations in rat brain presynaptic dopaminergic mechanisms
Gordon, I., Weizman, R., Rosenne, E., & Rehavi, M. (1995) · Developmental Brain Research · doi:10.1016/0165-3806(94)00216-m · Cited by 21 · see citing works
Barilar, J. O., Knezović, A., Perhoč, A. B., Homolak, J., Riederer, P. F., & Šalković‐Petrišić, M. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02152-8 · Cited by 22 · see citing works
[123I] β-CIT binding and SPET compared with clinical diagnosis in parkinsonism
Staffen, W., Mair, A., Unterrainer, J. M., et al. (2000) · Nuclear Medicine Communications · doi:10.1097/00006231-200005000-00002 · Cited by 16 · see citing works
Reduced Number of Caudate Nucleus Dopamine Uptake Sites in Vascular Dementia
Allard, P. O., Englund, E. M., & Marcusson, J. O. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017105 · Cited by 16 · see citing works
Self-citationUnchanged density of caudate nucleus dopamine uptake sites in depressed suicide victims
Allard, P. O., & Norl�n, M. (1997) · Journal of Neural Transmission · doi:10.1007/bf01294736 · Cited by 16 · see citing works
Self-citationKemppainen, N. M., Röyttä, M., Collan, Y. U., et al. (2001) · Acta Neuropathologica · doi:10.1007/s004010100425 · Cited by 15 · see citing works
“Previous studies on the dopaminergic system in patients with AD or AD with parkinsonism have demonstrated variable reductions in dopamine receptors [4, 5, 23] and a decreased number of striatal dopamine re-uptake sites [ 1 , 19, 24].”
Mechanism of Metal Complexes in Alzheimer’s Disease
Yi, L. I. U., Ma, J., Zhang, Q., Wang, Y., & Sun, Q. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211873 · Cited by 15 · see citing works
Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain
Bergström, K. A., Tupala, E., & Tiihonen, J. (2001) · Pharmacology & Toxicology · doi:10.1034/j.1600-0773.2001.880601.x · Cited by 14 · see citing works
Dopamine System Dysfunction in Alzheimer's Disease
Moreira, I. P., Vieira‐Coelho, M. A., & Guimarães, J. (2025) · Psychogeriatrics · doi:10.1111/psyg.70097 · Cited by 12 · see citing works
BindingDB (2012) · PubMed · doi:10.7270/q2x928vc · Cited by 12 · see citing works
Neuropharmacology and Receptor Studies in the Elderly
Meltzer, C. (1999) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/089198879901200307 · Cited by 12 · see citing works
Pharmacological interventions for apathy in Alzheimer's disease
Ruthirakuhan, M. T., Herrmann, N., Abraham, E. H., & Lanctôt, K. L. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012197 · Cited by 10 · see citing works
Loc’h, C., Müller, L., Ottaviani, M., et al. (1995) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.2580360412 · Cited by 9 · see citing works
Preparation of 99mTc-TRODAT-1 with high labeling yield in boiling water bath: A new formulation
Erfani, M., & Shafiei, M. (2014) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2014.01.003 · Cited by 8 · see citing works
“A significant reduction in the density of these transporters has been reported in patients with Parkinson’s and Alzheimer’s diseases [2–4].”
Background[3H]GBR 12935 labels mainly the piperazine acceptor site in the rat prefrontal cortex
Gordon, I., Weizman, R., & Rehavi, M. (1995) · Brain Research · doi:10.1016/0006-8993(95)00007-d · Cited by 8 · see citing works
Galinier, E., Garreau, L., Dognon, A. M., et al. (1993) · European Journal of Medicinal Chemistry · doi:10.1016/0223-5234(93)90047-i · Cited by 7 · see citing works
New preparation of [123I]PE2I: investigation of the oxidation and purification steps
Berthommier, E., Loc’h, C., Chalon, S., et al. (2002) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.620 · Cited by 6 · see citing works
Gordon, I., Weizman, R., & Rehavi, M. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00879-5 · Cited by 6 · see citing works
Mukhin, V. N., Borovets, I. R., Sizov, V. V., Pavlov, K. I., & Клименко, В. М. (2021) · Neurotoxicity Research · doi:10.1007/s12640-021-00371-9 · Cited by 4 · see citing works
“1 3 loss of dopamine binding sites in these brain structures (Allard et al. 1990; Murray et al. 1995; Rinne et al. 1998).”
Backgroundβ-Amyloid 25–35 Suppresses the Secretory Activity of the Dopaminergic System in the Rat Brain
Mukhin, V. N., Sizov, V. V., Pavlov, K. I., & Клименко, В. М. (2019) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-019-00807-y · Cited by 5 · see citing works
DEVELOPMENT OF A FREEZE-DRIED RADIOPHARMACEUTICAL KIT FOR DOPAMINE TRANSPORTERS IMAGING
Erfani, M., Shafiei, M., Charkhlooie, G. A., & Goudarzi, M. (2015) · Iranian Journal of Nuclear Medicine · Cited by 5 · see citing works
Garreau, L., Emond, P., Belzung, C., et al. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36808-9 · Cited by 5 · see citing works
Galinier, E., Ombetta, J., FRANGIN, Y., et al. (1994) · Journal of Labelled Compounds and Radiopharmaceuticals · doi:10.1002/jlcr.2580340512 · Cited by 5 · see citing works
Clinical and Neurochemical Aspects of Diseases with Cognitive Impairment
Gottfries, C. G. (1992) · Reviews in the Neurosciences · doi:10.1515/revneuro.1992.3.3.191 · Cited by 5 · see citing works
Self-citationKärkkäinen, E., Yavich, L., Miettinen, P. O., & Tanila, H. (2015) · Brain Research · doi:10.1016/j.brainres.2015.07.006 · Cited by 4 · see citing works
[14] Specificity and ion dependence of binding of GBR analogs
Corera, A. T., do Rego, J., & Bonnet, J. (1998) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(98)96016-5 · Cited by 4 · see citing works
Kim, H., Lee, D., Pyatha, S., & Kim, K. (2026) · Frontiers in Public Health · doi:10.3389/fpubh.2026.1801968 · Cited by 3 · see citing works
Mukhin, V. N., Borovets, I. R., Sizov, V. V., & Клименко, В. М. (2024) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093024010125 · Cited by 2 · see citing works
“The lack of evidence of decreased dopamine reuptake corroborates that the decrease of dopamine binding sites [66] or decline of DAT activity [67] in the putamen of patients is due to the degeneration of dopaminergic neurites, and not to a decrease of dopamine transporter protein units on the…”
Buyukiscan, E. S., Yıldırım, E., Demirtaş-Tatlıdede, A., Bılgıç, B., & Gurvit, H. I. (2023) · Experimental Aging Research · doi:10.1080/0361073x.2023.2256629 · Cited by 1 · see citing works
“In addition, a reduction in the expression of dopamine receptors in the nucleus accumbens (NAcc) and ventral tegmental area, as well as atrophy of the NAcc, have been reported in AD (Allard et al., 1990; Martorana & Ve Koch, 2014; Pievani et al., 2013).”
Caudate Nucleus Dopamine D2 Receptors in Vascular Dementia
Allard, P. O., Englund, E. M., & Marcusson, J. O. (2002) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000058329 · Cited by 1 · see citing works
Self-citationStörungen der monoaminergen Neurotransmittersysteme bei Demenz vom Alzheimer-Typ
Gottfries, C. G. (1992) · Springer eBooks · doi:10.1007/978-3-642-76932-0_9 · Cited by 1 · see citing works
Self-citationChau, S. A. (2013) · TSpace (University of Toronto)
- Authors
- Allard, P., Alafuzoff, I., Carlsson, A., Eriksson, K., Ericson, E., Gottfries, C.-G., & Marcusson, J. O.
- Affiliations
- Umeå University (SE)
- Karolinska Institutet (SE)
- University of Gothenburg (SE)
- Venue
- European Neurology
- Publisher
- S. Karger AG
- Published
- 2008-02-14
- Volume
- 30
- Issue
- 4
- Pages
- 181-185
- ISSN
- 0014-3022 (ISSN-L)
- 1421-9913
- OpenAlex
- W2074882701
- Cited by
- 64
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 2
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- Alzheimer's disease, senile dementia of the Alzheimer type, vascular dementia, dopamine uptake, putamen, dopamine transporter, dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid
- MeSH terms
- Aged, Alzheimer Disease, Dopamine, Female, Homovanillic Acid, Humans, Kinetics, Ligands, Male, Methyltyrosines, Middle Aged, Piperazines, Putamen, Receptors, Dopamine, alpha-Methyltyrosine, In Vitro Techniques
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