Discussion
COSMC coding mutations significantly diminished T-synthase activity in advanced AD, potentially causing defective galactosylation.
Methods
Identification of COSMC mutations, Real-Time Quantitative Reverse Transcription PCR (Q-RT-PCR), western blotting, and T-synthase activity assays.
Results
COSMC mutations were detected in the promotor, coding region and 3'UTR in AD and normals. COSMC coding mutations demonstrated a correlation with AD progression. T-synthase levels were significantly elevated in advanced AD compared to AD III (P = 0.03) and normals (P = 0.002). T-synthase activity in advanced AD {Braak and Braak (B&B) stages V and VI} with COSMC coding mutations was 3-fold lower than advanced AD without mutations, and 1.3-fold lower than normal (P = 0.001) and AD B&B stage III (P = 0.01) with coding mutations.