Gollamudi Seema, Lekhraj Rukmani, Lalezari Shirin, Lalezari Parviz
Neurosurgery Research Laboratory Department of Neurosurgery Montefiore Medical Center and Albert Einstein College of Medicine Bronx New York USA.
Alzheimers Dement (N Y). 2020 Jun 26;6(1):e12040. doi: 10.1002/trc2.12040. eCollection 2020.
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 / mutations in AD and age-matched normals without AD. The coding mutations resulted in a significant reduction in T-synthase activity in advanced AD cases.
Identification of mutations, Real-Time Quantitative Reverse Transcription PCR (Q-RT-PCR), western blotting, and T-synthase activity assays.
mutations were detected in the promotor, coding region and 3'UTR in AD and normals. coding mutations demonstrated a correlation with AD progression. T-synthase levels were significantly elevated in advanced AD compared to AD III ( = 0.03) and normals ( = 0.002). T-synthase activity in advanced AD {Braak and Braak (B&B) stages V and VI} with coding mutations was 3-fold lower than advanced AD without mutations, and 1.3-fold lower than normal ( = 0.001) and AD B&B stage III ( = 0.01) with coding mutations.
coding mutations significantly diminished T-synthase activity in advanced AD, potentially causing defective galactosylation.
随年龄积累的脑组织突变可能导致阿尔茨海默病（AD）。AD中已证实存在异常糖蛋白和Tn抗原表达。我们在AD患者及年龄匹配的非AD正常个体中鉴定了[未提及具体基因名称]突变。这些编码突变导致晚期AD病例中T合酶活性显著降低。
[未提及具体基因名称]突变鉴定、实时定量逆转录PCR（Q-RT-PCR）、蛋白质印迹法及T合酶活性测定。
在AD患者和正常个体的启动子、编码区及3'非翻译区（UTR）检测到[未提及具体基因名称]突变。编码突变与AD进展相关。与AD III期（P = 0.03）和正常个体（P = 0.002）相比，晚期AD患者的T合酶水平显著升高。存在编码突变的晚期AD患者{Braak和Braak（B&B）分期V和VI期}的T合酶活性比无突变的晚期AD患者低3倍，比正常个体（P = 0.001）和存在编码突变的AD B&B分期III期（P = 0.01）低1.3倍。
编码突变显著降低了晚期AD患者的T合酶活性，可能导致半乳糖基化缺陷。
