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Abstract Introduction Mutations in brain tissues that cumulate with age may contribute to Alzheimer's disease (AD). Abnormal glycoprotein and Tn antigen expression have been demonstrated in AD. We identified C1GALT1C1/COSMC mutations in AD and age‐matched normals without AD. The COSMC coding mutations resulted in a significant reduction in T‐synthase activity in advanced AD cases. 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. Discussion COSMC coding mutations significantly diminished T‐synthase activity in advanced AD, potentially causing defective galactosylation.

Introduction: Mutations in brain tissues that cumulate with age may contribute to Alzheimer's disease (AD). Abnormal glycoprotein and Tn antigen expression have been demonstrated in AD. We identified C1GALT1C1 / COSMC mutations in AD and age-matched normals without AD. The COSMC coding mutations resulted in a significant reduction in T-synthase activity in advanced AD cases., 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., Discussion: COSMC coding mutations significantly diminished T-synthase activity in advanced AD, potentially causing defective galactosylation., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)