Spinocerebellar ataxia type 3 (SCA3): thalamic neurodegeneration occurs independently from thalamic ataxin-3 immunopositive neuronal intranuclear inclusions.
In the last years progress has been made regarding the involvement of the thalamus during the course of the currently known polyglutamine diseases. Although recent studies have shown that the thalamus consistently undergoes neurodegeneration in Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2) it is still unclear whether it is also a consistent target of the pathological process of spinocerebellar ataxia type 3 (SCA3). Accordingly we studied the thalamic pathoanatomy and distribution pattern of ataxin-3 immunopositive neuronal intranuclear inclusions (NI) in nine clinically diagnosed and genetically confirmed SCA3 patients and carried out a detailed statistical analysis of our findings. During our pathoanatomical study we disclosed (i) a consistent degeneration of the ventral anterior, ventral lateral and reticular thalamic nuclei; (ii) a degeneration of the ventral posterior lateral nucleus and inferior and lateral subnuclei of the pulvinar in the majority of these SCA3 patients; and (iii) a degeneration of the ventral posterior medial and lateral posterior thalamic nuclei, the lateral geniculate body and some of the limbic thalamic nuclei in some of them. Upon immunocytochemical analysis we detected NI in all of the thalamic nuclei of all of our SCA3 patients. According to our statistical analysis (i) thalamic neurodegeneration and the occurrence of ataxin-3 immunopositive thalamic NI was not associated with the individual length of the CAG-repeats in the mutated SCA3 allele, the patients age at disease onset and the duration of SCA3 and (ii) thalamic neurodegeneration was not correlated with the occurrence of ataxin-3 immunopositive thalamic NI. This lack of correlation may suggest that ataxin-3 immunopositive NI are not immediately decisive for the fate of affected nerve cells but rather represent unspecific and pathognomonic morphological markers of SCA3.
Rüb
Udo
U
Institute for Clinical Neuroanatomy, Johann Wolfgang Goethe-Univeristy, Frankfurt-Main, Germany.
de Vos
Rob A I
RA
Brunt
Ewout R
ER
Sebestény
Tamás
T
Schöls
Ludger
L
Auburger
Georg
G
Bohl
Jürgen
J
Ghebremedhin
Estifanos
E
Gierga
Kristin
K
Seidel
Kay
K
den Dunnen
Wilfred
W
Heinsen
Helmut
H
Paulson
Henry
H
Deller
Thomas
T
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000067699:Ataxin-3; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism / Q000473:pathology*; D017827:Machado-Joseph Disease / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism / Q000473:pathology*; D018911:Trinucleotide Repeats / Q000235:genetics
D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C092341:ATXN3 protein, human; D000067699:Ataxin-3