Department of Geriatric Medicine, All India Institute of Medical Sciences, New Delhi, India.
Department of Nuclear Medicines, All India Institute of Medical Sciences, New Delhi, India.
Mech Ageing Dev. 2020 Sep;190:111290. doi: 10.1016/j.mad.2020.111290. Epub 2020 Jun 27.
Diagnosis of Alzheimer's disease (AD) is often difficult because of distinct and subjective clinical features, especially in the early stage. FOXO3a protein present in the cognitive centre of brain in inferior temporal region and parahippocampus. FOXO3a can be a potential novel target against AD. AD, Mild Cognitive impairment (MCI) and Geriatric Control (GC) were recruited after diagnosis by clinical assessment, MRI, TauPET and FDG-PET. We have quantified serum FOXO3a by surface plasmon resonance (SPR) and compare with TauPET between of AD, MCI patients and GC. Serum FOXO3A was significantly lower in AD (1.42 ± 0.09 ng/μl) compare to MCI (1.61 ± 0.14 ng/μl) and GC (1.89 ± 0.07 ng/μl). However, the Tau was higher in AD both in serum and also in PET scan. Serum pTau was significantly over-expressed in AD (0.176 ± 0.03 ng/μl), compare to other groups; MCI (0.16 ± 0.014 ng/μl) and GC (0.15 ± 0.024 ng/μl). Serum FOXO3A could significantly differentiate AD vs MCI, MCI vs GC and AD vs GC. However, Tau protein could only differentiate AD vs GC but not MCI vs GC. Serum FOXO3A may serve as novel blood marker for early detection for AD and target for therapeutic intervention.
阿尔茨海默病(AD)的诊断通常很困难,因为其具有独特且主观的临床特征,尤其是在早期阶段。FOXO3a 蛋白存在于大脑下颞叶和海马旁回的认知中心。FOXO3a 可以成为针对 AD 的潜在新靶点。AD、轻度认知障碍(MCI)和老年对照组(GC)在通过临床评估、MRI、TauPET 和 FDG-PET 诊断后招募。我们通过表面等离子体共振(SPR)定量了血清 FOXO3a,并将其与 AD、MCI 患者和 GC 之间的 TauPET 进行了比较。AD 患者的血清 FOXO3A 明显低于 MCI(1.61±0.14ng/μl)和 GC(1.89±0.07ng/μl)(1.42±0.09ng/μl)。然而,AD 患者的 Tau 在血清和 PET 扫描中均升高。AD 患者的血清 pTau 明显过表达(0.176±0.03ng/μl),与其他组相比;MCI(0.16±0.014ng/μl)和 GC(0.15±0.024ng/μl)。血清 FOXO3A 可显著区分 AD 与 MCI、MCI 与 GC 以及 AD 与 GC,但 Tau 蛋白只能区分 AD 与 GC,而不能区分 MCI 与 GC。血清 FOXO3A 可能成为 AD 早期检测的新型血液标志物和治疗干预的靶点。