Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 8/2016

01-10-2016 | Original Article

Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study

Authors: Tatsuhiro Terada, Masamichi Yokokura, Etsuji Yoshikawa, Masami Futatsubashi, Satoshi Kono, Takashi Konishi, Hiroaki Miyajima, Takanori Hashizume, Yasuomi Ouchi

Published in: Annals of Nuclear Medicine | Issue 8/2016

Login to get access

Abstract

Background

The neuroinflammatory glial response contributes to the degenerative process in Parkinson’s disease (PD). However, the pattern of microglial progression remains unclear.

Methods

We evaluated microglial activation in early stage PD patients by quantifying changes in neuroinflammation using PET with [11C]DPA713, a selective PET tracer for microglial activation. Eleven PD patients (Hoehn and Yahr stages 1–2) without dementia underwent the [11C]DPA713 PET scan two times with 1 year apart. The binding potential (BPND) was estimated with the simplified reference tissue model. Voxelwise and regions of interest analyses were used to compare the regional BPND among groups.

Results

Significant increase in [11C]DPA713 BPND was found extrastriatally in the occipital, temporal and parietal cortex in PD patients, and the degree of BPND became much higher over the brain regions predominantly in the temporal and occipital cortex 1 year later.

Conclusion

The current results indicated that an extrastriatal spreading of microglial activation reflects one of PD pathophysiology occurring at an early stage.
Appendix
Available only for authorised users
Literature
1.
Muller CM, de Vos RA, Maurage CA, Thal DR, Tolnay M, Braak H. Staging of sporadic Parkinson disease-related alpha-synuclein pathology: inter- and intra-rater reliability. J Neuropathol Exp Neurol. 2005;64:623–8.CrossRefPubMed
2.
Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, et al. Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol. 2005;57:168–75.CrossRefPubMed
3.
Banati RB, Daniel SE, Blunt SB. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson’s disease. Mov Disord. 1998;13:221–7.CrossRefPubMed
4.
McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology. 1988;38:1285–91.CrossRefPubMed
5.
Ouchi Y, Yagi S, Yokokura M, Sakamoto M. Neuroinflammation in the living brain of Parkinson’s disease. Parkinsonism Relat Disord. 2009;15(Suppl 3):S200–4.CrossRefPubMed
6.
Mrak RE, Griffin WS. Common inflammatory mechanisms in Lewy body disease and Alzheimer disease. J Neuropathol Exp Neurol. 2007;66:683–6.CrossRefPubMed
7.
Iannaccone S, Cerami C, Alessio M, Garibotto V, Panzacchi A, Olivieri S, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19:47–52.CrossRefPubMed
8.
Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis. 2006;21:404–12.CrossRefPubMed
9.
Edison P, Ahmed I, Fan Z, Hinz R, Gelosa G, Ray Chaudhuri K, et al. Microglia, amyloid, and glucose metabolism in Parkinson’s disease with and without dementia. Neuropsychopharmacology. 2013;38:938–49.CrossRefPubMedPubMedCentral
10.
Bartels AL, Willemsen AT, Doorduin J, de Vries EF, Dierckx RA, Leenders KL. [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson’s disease? Parkinsonism Relat Disord. 2010;16:57–9.CrossRefPubMed
11.
Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere JJ, Lindemann P, et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402–9.CrossRefPubMed
12.
Yokokura M. Depiction of microglial activation in the living human brain by different TSPO tracers. Abstr Soc Neurosci; 2013; San Diego, USA.
13.
Hagell P, Nilsson MH. The 39-item Parkinson’s Disease Questionnaire (PDQ-39): is it a unidimensional construct? Ther Adv Neurol Disord. 2009;2:205–14.CrossRefPubMedPubMedCentral
14.
Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992;40:922–35.CrossRefPubMed
15.
Holmes CB, Fouty HE, Wurtz PJ, Burdick BM. Zung Self-Rating Depression Scale scores of psychiatric outpatients by age and sex. Psychol Rep. 1988;62:259–62.CrossRefPubMed
16.
McKeith IG, Dickson DW, Lowe J, Emre M, O’Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65:1863–72.CrossRefPubMed
17.
Maeda T, Takano D, Yamazaki T, Satoh Y, Nagata K. Zonisamide in the early stage of Parkinson’s disease. Neurol Clin Neurosci. 2015;3:127–30.CrossRef
18.
Okada H, Ouchi Y, Ogawa M, Futatsubashi M, Saito Y, Yoshikawa E, et al. Alterations in alpha4beta2 nicotinic receptors in cognitive decline in Alzheimer’s aetiopathology. Brain. 2013;136:3004–17.CrossRefPubMed
19.
Yokokura M, Terada T, Bunai T, Nakaizumi K, Takebayashi K, Iwata Y, et al. Depiction of microglial activation in aging and dementia: Positron emission tomography 11CDPA713 versus 11C PK11195. J Cereb Blood Flow Metab. 2016;. doi:10.​1177/​0271678X16646788​.PubMed
20.
Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage. 1996;4:153–8.CrossRefPubMed
21.
Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2011;38:343–51.CrossRefPubMed
22.
Yagi S, Yoshikawa E, Futatsubashi M, Yokokura M, Yoshihara Y, Torizuka T, et al. Progression from unilateral to bilateral parkinsonism in early Parkinson disease: implication of mesocortical dopamine dysfunction by PET. J Nucl Med. 2010;51:1250–7.CrossRefPubMed
23.
Grover ND, Limaye RP, Gokhale DV, Patil TR. Zonisamide: a review of the clinical and experimental evidence for its use in Parkinson’s disease. Indian J Pharmacol. 2013;45:547–55.CrossRefPubMedPubMedCentral
24.
Asanuma M, Miyazaki I, Diaz-Corrales FJ, Kimoto N, Kikkawa Y, Takeshima M, et al. Neuroprotective effects of zonisamide target astrocyte. Ann Neurol. 2010;67:239–49.CrossRefPubMed
25.
Choudhury ME, Moritoyo T, Kubo M, Kyaw WT, Yabe H, Nishikawa N, et al. Zonisamide-induced long-lasting recovery of dopaminergic neurons from MPTP-toxicity. Brain Res. 2011;1384:170–8.CrossRefPubMed
26.
Yokoyama H, Yano R, Kuroiwa H, Tsukada T, Uchida H, Kato H, et al. Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) neurotoxicity in mice. Metab Brain Dis. 2010;25:305–13.CrossRefPubMed
27.
Murata M, Horiuchi E, Kanazawa I. Zonisamide has beneficial effects on Parkinson’s disease patients. Neurosci Res. 2001;41:397–9.CrossRefPubMed
28.
Ji B, Maeda J, Sawada M, Ono M, Okauchi T, Inaji M, et al. Imaging of peripheral benzodiazepine receptor expression as biomarkers of detrimental versus beneficial glial responses in mouse models of Alzheimer’s and other CNS pathologies. J Neurosci. 2008;28:12255–67.CrossRefPubMedPubMedCentral
29.
Dickens AM, Vainio S, Marjamaki P, Johansson J, Lehtiniemi P, Rokka J, et al. Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med. 2014;55:466–72.CrossRefPubMed
Metadata
Title
Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study
Authors
Tatsuhiro Terada
Masamichi Yokokura
Etsuji Yoshikawa
Masami Futatsubashi
Satoshi Kono
Takashi Konishi
Hiroaki Miyajima
Takanori Hashizume
Yasuomi Ouchi
Publication date
01-10-2016
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 8/2016
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-016-1099-2

Other articles of this Issue 8/2016

Annals of Nuclear Medicine 8/2016 Go to the issue

Original Article

Functional volumetric analysis of striatum using F-18 FP-CIT PET in patients with idiopathic Parkinson’s disease and normal subjects

Original Article

Impact of patient age on the iodine/FDG “flip-flop” phenomenon in lung metastasis from thyroid cancer

Original Article

The utility of PET/CT with 68Ga-DOTATOC in sarcoidosis: comparison with 67Ga-scintigraphy

Original Article

A two‐center study for the quality control of [18F]FDG using FASTlab phosphate cassettes

Original Article

Effect of 18F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses

Original Article

18F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes