Decreased dopamine transporter binding in Machado-Joseph disease.

Abstract

UNLABELLED:

The aim of this study was to use 99mTc-TRODAT-1 brain SPECT for investigation of the binding of dopamine transporter (DAT) in the nigrostriatal dopaminergic pathway of symptomatic Machado-Joseph disease (MJD) and to compare the results with the abnormal cytidylate, adenylate, and guanylate (CAG) expansion in the MJD1 gene and other clinical factors.

METHODS:

Ten symptomatic MJD patients (8 women, 2 men; age range, 20-71 y; mean age +/- SD, 36.4 +/- 10.6 y; mean duration of illness, 9.8 +/- 5.4 y) and 21 healthy volunteers (age range, 24-71 y; mean age, 47.6 +/- 20.1 y) were examined. Brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific nigrostriatal 99mTc-TRODAT-1 binding was measured and compared with the clinical symptoms, duration of illness, and size of abnormal expanded CAG repeats.

RESULTS:

All nigrostriatal 99mTc-TRODAT-1 ratios were significantly lower in MJD patients than in healthy volunteers (P < 0.05). Discriminant function analysis of all MJD patients showed that the decreased binding of 99mTc-TRODAT-1 in the putamen was not significantly different from that in the caudate nucleus. Eight of 10 MJD patients had significantly decreased 99mTc-TRODAT-1 uptake. Of these 8, 2 had extrapyramidal signs and 6 had no obvious extrapyramidal signs. The other 2 patients, who had normal 99mTc-TRODAT-1 uptake, had no obvious extrapyramidal signs.

CONCLUSION:

Our findings indicate that 99mTc-TRODAT-1 brain SPECT is an appropriate method for evaluating damage to the nigrostriatal DAT in symptomatic MJD patients with and without extrapyramidal signs. The decreased binding of 99mTc-TRODAT-1 in the nigrostriatal dopaminergic pathway in symptomatic MJD patients correlates with the phenotype of extrapyramidal signs but not with the abnormal CAG repeat length, age at disease onset, or disease duration.

• Authors: T C Yen, C S Lu, K Y Tzen, S P Wey, Y H Chou, Y H Weng, P F Kao, G Ting
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 41 Issue 6 Pg. 994-8 (Jun 2000) ISSN: 0161-5505 [Print] United States
• PMID: 10855623 (Publication Type: Journal Article)

Chemical References

• Carrier Proteins
• Dopamine Plasma Membrane Transport Proteins
• Membrane Glycoproteins
• Membrane Transport Proteins
• Nerve Tissue Proteins
• Organotechnetium Compounds
• SLC6A3 protein, human
• Tropanes
• technetium Tc 99m TRODAT-1
• Dopamine

Topics

• Adolescent
• Adult
• Aged
• Brain (diagnostic imaging, metabolism)
• Carrier Proteins (metabolism)
• Caudate Nucleus (diagnostic imaging, metabolism)
• Child
• Dopamine (metabolism)
• Dopamine Plasma Membrane Transport Proteins
• Female
• Humans
• Machado-Joseph Disease (diagnostic imaging, metabolism)
• Male
• Membrane Glycoproteins
• Membrane Transport Proteins
• Middle Aged
• Nerve Tissue Proteins
• Organotechnetium Compounds
• Putamen (diagnostic imaging, metabolism)
• Substantia Nigra (metabolism)
• Tomography, Emission-Computed, Single-Photon
• Trinucleotide Repeat Expansion
• Tropanes