Spinocerebellar ataxia 12 (SCA12) is a unique dominant type of
ataxia characterized by early and prominent
action tremors,
memory deficit, neuropathy,
dysarthria, etc. The expansion of
DNA triplet (CAG) repeats in
5'UTR of PPP2R2B gene appears to be the cause for the pathogenesis of the
neurodegenerative disorder, SCA12. The objective of the current study was to identify the aberrantly expressed
plasma proteins for their potential application in
therapy or diagnosis/prognosis of SCA12. Sixty-two clinically suspected patients were assessed using International Co-operative
Ataxia Rating Scale (ICARS) and genetic confirmation was done using PCR followed by
DNA sequencing. Twenty patients who were genetically confirmed were included in the study. 2D-DIGE analyses of
plasma proteins of SCA12 patients revealed 14 differentially expressed
protein spots, which were confirmed as nine
proteins by LC-MS/MS. The 6 downregulated and 3 upregulated
proteins are known to have physiological role in transport (
thyroxin and
retinol to brain), lipid metabolism, memory, scavenging of free haemoglobin, etc. Altered expression of some of the
proteins of interest,
transthyretin, haptaglobin,
apolipoprotein C-II,
apolipoprotein C-III are indicative of clinical manifestations such as neuropathy,
cognitive impairment and altered lipid metabolism in SCA12.