Abstract
In Parkinson’s disease (PD), there is degeneration of the cholinergic, noradrenergic, and serotonergic systems in addition to dopaminergic projections. Function of these non-dopaminergic systems can be imaged with positron emission tomography (PET) and single photon emission computed tomography (SPECT) and correlated with motor and nonmotor symptomatology. In addition, neuronal loss in PD is associated with microglial activation. The role of microglia in driving the disease process remains uncertain. This review presents and discusses current findings in these areas.
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References
Jellinger K (1987) The pathology of parkinsonism. In: Marsden CD, Fahn S (eds) Movement disorders 2. London: Butterworths, pp 124–165
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) The accuracy of the clinical diagnosis of Parkinson’s disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Litvan I, Macintyre A, Goetz CG, Wenning GK, Jellinger K, Verny M, Bartko JJ, Jankovic J, Mckee A, Brandel JP, Chaudhuri KR, Lai EC, D’olhaberriague L, Pearce RKB, Agid Y (1998) Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies. Arch Neurol 55:969–978, Jul
McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872
McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291
Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol (Berl) 106:518–526
Lamarre Y (1984) Animal models of tremor. In: Findley LJ, Capildeo R (eds) Movement disorders: tremor. London: MacMillan Press, pp 183–194
Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ (2003) Tremor in Parkinson’s disease and serotonergic dysfunction: an (11)C-WAY 100635 PET study. Neurology 60:601–605
Doder M, Rabiner EA, Turjanski N, Lees AJ, Brooks DJ (2000) Brain serotonin HT1A receptors in Parkinson’s disease with and without depression measured by positron emission tomography and 11C-WAY100635. In: Movement disorders. vol 15 Supp 3. 213
Mayberg HS, Starkstein SE, Sadzot B, Preziosi T, Andrezejewski PL, Dannals RF, Wagner HN, Jr, Robinson RG (1990) Selective hypometabolism in the inferior frontal lobe in depressed patients with Parkinson’s disease. Ann Neurol 28:57–64
Kim SE, Choi JY, Choe YS, Choi Y, Lee WY (2003) Serotonin transporters in the midbrain of Parkinson’s disease patients: a study with 123I-beta-CIT SPECT. J Nucl Med 44:870–876
Becker G, Berg D, Lesch KP, Becker T (2001) Basal limbic system alteration in major depression: a hypothesis supported by transcranial sonography and MRI findings. Int J Neuropsychopharmacol 4:21–31
Berg D, Supprian T, Hofmann E, Zeiler B, Jager A, Lange KW, Reiners K, Becker T, Becker G (1999) Depression in Parkinson’s disease: brainstem midline alteration on transcranial sonography and magnetic resonance imaging. J Neurol 246:1186–1193
Ding YS, Lin KS, Logan J, Benveniste H, Carter P (2005) Comparative evaluation of positron emission tomography radiotracers for imaging the norepinephrine transporter: (S,S) and (R,R) enantiomers of reboxetine analogs ([11C]methylreboxetine, 3-Cl-[11C]methylreboxetine and [18F]fluororeboxetine), (R)-[11C]nisoxetine, [11C]oxaprotiline and [11C]lortalamine. J Neurochem 94:337–351
Ding YS, Lin KS, Garza V, Carter P, Alexoff D, Logan J, Shea C, Xu Y, King P (2003) Evaluation of a new norepinephrine transporter PET ligand in baboons, both in brain and peripheral organs. Synapse 50:345–352
Remy P, Doder M, Lees AJ, Turjanski N, Brooks DJ (2005) Depression in Parkinson’s disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain 128:1314–1322
Kuhl DE, Minoshima S, Fessler JA, Frey KA, Foster NL, Ficaro EP, Wieland DM, Koeppe RA (1996) In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol 40:399–410
Asahina M, Suhara T, Shinotoh H, Inoue O, Suzuki K, Hattori T (1998) Brain muscarinic receptors in progressive supranuclear palsy and Parkinson’s disease: a positron emission tomographic study. J Neurol Neurosurg Psychiatry 65:155–163
Bohnen NI, Kaufer DI, Ivanco LS, Lopresti B, Koeppe RA, Davis JG, Mathis CA, Moore RY, DeKosky ST (2003) Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol 60:1745–1748
Bohnen NI, Kaufer DI, Hendrickson R, Ivanco LS, Lopresti BJ, Constantine GM, Mathis CA, Davis JG, Moore RY, Dekosky ST (2005) Cognitive correlates of cortical cholinergic denervation in Parkinson’s disease and parkinsonian dementia. J Neurol 253:242–247
Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 57:168–175
Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006) In vivo imaging of microglial activation with [(11)C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21:404–412
Jolkkonen J, Jenner P, Marsden CD (1995) l-dopa reverses altered gene expression of substance P but not enkephalin in the caudate–putamen of common marmosets treated with MPTP. Mol Brain Res 32:297–307
Jones AK, Watabe H, Cunningham VJ, Jones T (2004) Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by [11C]diprenorphine binding and PET. Eur J Pain 8:479–485
Piccini P, Weeks RA, Brooks DJ (1997) Opioid receptor binding in Parkinson’s patients with and without levodopa-induced dyskinesias. Ann Neurol 42:720–726
Whone AL, Rabiner EA, Arahata Y, Luthra SK, Hargreaves R, Brooks DJ (2002) Reduced substance P binding in Parkinson’s disease complicated by dyskinesias: an F-18-L829165 PET study. Neurology 58:A488–A489
Yoshita M (2000) Cardiac uptake of [123I]MIBG separates PD from multiple system atrophy. Neurology 54:1877–1878
Druschky A, Hilz MJ, Platsch G, Radespiel-Troger M, Druschky K, Kuwert T, Neundorfer B (2000) Differentiation of Parkinson’s disease and multiple system atrophy in early disease stages by means of I-123-MIBG-SPECT. J Neurol Sci 175:3–12
Reinhardt MJ, Jungling FD, Krause TM, Braune S (2000) Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake. Eur J Nucl Med 27:595–600
Courbon F, Brefel-Courbon C, Thalamas C, Alibelli MJ, Berry I, Montastruc JL, Rascol O, Senard JM (2003) Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson’s disease. Mov Disord 18:890–897
Satoh A, Serita T, Seto M, Tomita I, Satoh H, Iwanaga K, Takashima H, Tsujihata M (1999) Loss of 123I-MIBG uptake by the heart in Parkinson’s disease: assessment of cardiac sympathetic denervation and diagnostic value. J Nucl Med 40:371–375
Braune S, Reinhardt M, Schnitzer R, Riedel A, Lucking CH (1999) Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy. Neurology 53:1020–1025
Yoshita M (1998) Differentiation of idiopathic Parkinson’s disease from striatonigral degeneration and progressive supranuclear palsy using iodine-123 meta-iodobenzylguanidine myocardial scintigraphy. J Neurol Sci 155:60–67
Hirayama M, Hakusui S, Koike Y, Ito K, Kato T, Ikeda M, Hasegawa Y, Takahashi A (1995) A scintigraphical qualitative analysis of peripheral vascular sympathetic function with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure. J Auton Nerv Syst 53:230–234
Berding G, Schrader CH, Peschel T, van den Hoff J, Kolbe H, Meyer GJ, Dengler R, Knapp WH (2003) [N-methyl 11C]meta-Hydroxyephedrine positron emission tomography in Parkinson’s disease and multiple system atrophy. Eur J Nucl Med Mol Imaging 30:127–131
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Brooks, D.J. Imaging Non-Dopaminergic Function in Parkinson’s Disease. Mol Imaging Biol 9, 217–222 (2007). https://doi.org/10.1007/s11307-007-0084-5
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DOI: https://doi.org/10.1007/s11307-007-0084-5