Brain, Vol. 122, No. 8, 1449-1468,
August 1999
© 1999 Oxford University Press
Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer's and Parkinson's diseases: rostrocaudal distribution
1 MRC Neurochemical Pathology Unit, 2 Department of Neuropathology, 3 Old Age Psychiatry, Newcastle General Hospital, 4 Department of Psychiatry Research Unit, University of Newcastle-upon-Tyne Medical School and 5 Department of Neurology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
Correspondence to:
M. A. Piggott, MRC Neurochemical Pathology Unit, Westgate Road, Newcastle General Hospital, Newcastle-upon-Tyne, NE4 6BE, UK E-mail: M.A.Piggott{at}ncl.ac.uk
Dementia with Lewy bodies (DLB) is a neuropsychiatric disease associated with extrapyramidal features which differ from those of Parkinson's disease, including reduced effectiveness of L-dopa and severe sensitivity reactions to neuroleptic drugs. Distinguishing Alzheimer's disease from DLB is clinically relevant in terms of prognosis and appropriate treatment. Dopaminergic activities have been investigated at coronal levels along the rostrocaudal striatal axis from a post-mortem series of 25 DLB, 14 Parkinson's disease and 17 Alzheimer's disease patients and 20 elderly controls. [3H]Mazindol binding to the dopamine uptake site was significantly reduced in the caudal putamen in DLB compared with controls (57%), but not as extensively as in Parkinson's disease (75%), and was unchanged in Alzheimer's disease. Among three dopamine receptors measured (D1, D2 and D3), the most striking changes were apparent in relation to D2. In DLB, [3H]raclopride binding to D2 receptors was significantly reduced in the caudal putamen (17%) compared with controls, and was significantly lower than in Parkinson's disease at all levels. D2 binding was significantly elevated at all coronal levels in Parkinson's disease compared with controls, most extensively in the rostral putamen (71%). There was no change from the normal pattern of D2 binding in Alzheimer's disease. The only significant alteration in D1 binding ([3H]SCH23390) in the groups examined was an elevation (30%) in the caudal striatum in Parkinson's disease. There were no differences in D3 binding, measured using [3H]7-OH-DPAT, in DLB compared with controls. A slight, significant decrease in D3 binding in the caudal striatum of Parkinson's disease (13%) patients and an increase in Alzheimer's disease (20%) in the dorsal striatum at the level of the nucleus accumbens were found. The concentration and distribution of dopamine were disrupted in both DLB and Parkinson's disease, although in the caudate nucleus the loss of dopamine in DLB was uniform whereas in Parkinson's disease the loss was greater caudally. In the caudal putamen, dopamine was reduced by 72% in DLB and by 90% in Parkinson's disease. The homovanillic acid : dopamine ratio, a metabolic index, indicated compensatory increased turnover in Parkinson's disease, which was absent in DLB despite the loss of substantia nigra neurons (49%), dopamine and uptake sites. These differences between DLB, Parkinson's disease and Alzheimer's disease may explain some characteristics of the extrapyramidal features of DLB and its limited response to L-dopa and severe neuroleptic sensitivity. The distinct changes in the rostrocaudal pattern of expression of dopaminergic parameters are relevant to the interpretation of the in vivo imaging and diagnosis of DLB.
human striatum; dementia with Lewy bodies; Alzheimer's disease; Parkinson's disease; dopamine receptors
ANOVA = analysis of variance; DLB = dementia with Lewy bodies; HVA = homovanillic acid; 7-OH-DPAT = R(+)-7-hydroxy-dipropylaminotetralin-2-N,N-di[2,3(n)-propylamino]-7-hydroxy-1,2,3,4-tetrahydronaphthalene; PPAP = R(–)-N-(3-propyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride; SCH23390 = R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. T. O'Brien, I. G. McKeith, Z. Walker, K. Tatsch, J. Booij, J. Darcourt, M. Marquardt, C. Reininger, and the DLB Study Group Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies The British Journal of Psychiatry, January 1, 2009; 194(1): 34 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-P. Taylor, S. J Colloby, I. G McKeith, D. J Burn, D. Williams, J. Patterson, and J. T O'Brien Cholinesterase inhibitor use does not significantly influence the ability of 123I-FP-CIT imaging to distinguish Alzheimer's disease from dementia with Lewy bodies J. Neurol. Neurosurg. Psychiatry, October 1, 2007; 78(10): 1069 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kim, J. Nam, and K. Kim Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain Human and Experimental Toxicology, September 1, 2007; 26(9): 741 - 746. [Abstract] [PDF]
|
|
|
|
|
|
N M Warren, M A Piggott, A J Lees, and D J Burn The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases J. Neurol. Neurosurg. Psychiatry, June 1, 2007; 78(6): 571 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Papapetropoulos Regional Alpha-Synuclein Aggregation, Dopaminergic Dysregulation, and the Development of Drug-Related Visual Hallucinations in Parkinson's Disease J Neuropsychiatry Clin Neurosci, May 1, 2006; 18(2): 149 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. G. McKeith, D. W. Dickson, J. Lowe, M. Emre, J. T. O'Brien, H. Feldman, J. Cummings, J. E. Duda, C. Lippa, E. K. Perry, et al. Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium Neurology, December 27, 2005; 65(12): 1863 - 1872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Molloy, I G McKeith, J T O'Brien, and D J Burn The role of levodopa in the management of dementia with Lewy bodies J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1200 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Koeppe, S. Gilman, A. Joshi, S. Liu, R. Little, L. Junck, M. Heumann, K. A. Frey, and R. L. Albin 11C-DTBZ and 18F-FDG PET Measures in Differentiating Dementias J. Nucl. Med., June 1, 2005; 46(6): 936 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. P. Mosimann, R. M. Muri, D. J. Burn, J. Felblinger, J. T. O'Brien, and I. G. McKeith Saccadic eye movement changes in Parkinson's disease dementia and dementia with Lewy bodies Brain, June 1, 2005; 128(6): 1267 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Aarsland, C. G. Ballard, and G. Halliday Are Parkinson's Disease with dementia and Dementia with lewy Bodies the Same Entity? J Geriatr Psychiatry Neurol, September 1, 2004; 17(3): 137 - 145. [Abstract] [PDF]
|
|
|
|
 |
|
 J. T. O'Brien, S. Colloby, J. Fenwick, E. D. Williams, M. Firbank, D. Burn, D. Aarsland, and I. G. McKeith Dopamine Transporter Loss Visualized With FP-CIT SPECT in the Differential Diagnosis of Dementia With Lewy Bodies Arch Neurol, June 1, 2004; 61(6): 919 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Cousins, E. J. Burton, D. Burn, A. Gholkar, I. G. McKeith, and J. T. O'Brien Atrophy of the putamen in dementia with Lewy bodies but not Alzheimer's disease: An MRI study Neurology, November 11, 2003; 61(9): 1191 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zarow, S. A. Lyness, J. A. Mortimer, and H. C. Chui Neuronal Loss Is Greater in the Locus Coeruleus Than Nucleus Basalis and Substantia Nigra in Alzheimer and Parkinson Diseases Arch Neurol, March 1, 2003; 60(3): 337 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z Walker, D C Costa, R W H Walker, K Shaw, S Gacinovic, T Stevens, G Livingston, P Ince, I G McKeith, and C L E Katona Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand J. Neurol. Neurosurg. Psychiatry, August 1, 2002; 73(2): 134 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Minoshima, N. L. Foster, E. C. Petrie, R. L. Albin, K. A. Frey, and D. E. Kuhl Neuroimaging in Dementia with Lewy Bodies: Metabolism, Neurochemistry, and Morphology J Geriatr Psychiatry Neurol, January 1, 2002; 15(4): 200 - 209. [Abstract] [PDF]
|
|
|
|
|
|
X. S. Hu, N. Okamura, H. Arai, M. Higuchi, T. Matsui, M. Tashiro, M. Shinkawa, M. Itoh, T. Ido, and H. Sasaki 18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies Neurology, November 28, 2000; 55(10): 1575 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. G. McKeith, C. G. Ballard, R. H. Perry, P. G. Ince, J. T. O'Brien, D. Neill, K. Lowery, E. Jaros, R. Barber, P. Thompson, et al. Prospective validation of Consensus criteria for the diagnosis of dementia with Lewy bodies Neurology, March 14, 2000; 54(5): 1050 - 1058. [Abstract] [Full Text] [PDF]
|
|