Department of Materials Science and Engineering, Stanford University, 496 Lomita Mall, Stanford, CA 94305, USA.
Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA 94305, USA.
Ultramicroscopy. 2021 Dec;231:113254. doi: 10.1016/j.ultramic.2021.113254. Epub 2021 Mar 16.
Abnormal accumulation of inorganic trace elements in a human brain, such as iron, zinc and aluminum, oftentimes manifested as deposits and accompanied by a chemical valence change, is pathologically relevant to various neurodegenerative diseases. In particular, Fe has been hypothesized to produce free radicals that induce oxidative damage and eventually cause Alzheimer's disease (AD). However, traditional biomedical techniques, e.g. histology staining, are limited in studying the chemical composition and valence states of these inorganic deposits. We apply commonly used physical (phys-) science methods such as X-ray energy dispersive spectroscopy (EDS), focused-ion beam (FIB) and electron energy loss spectroscopy (EELS) in transmission electron microscopy in conjunction with magnetic resonance imaging (MRI), histology and optical microscopy (OM) to study the valence states of iron deposits in AD patients. Ferrous ions are found in all deposits in brain tissues from three AD patients, constituting 0.22-0.50 of the whole iron content in each specimen. Such phys-techniques are rarely used in medical science and have great potential to provide unique insight into biomedical problems.
人类大脑中无机微量元素（如铁、锌、铝）的异常积累，通常表现为沉积物，并伴有化学价态变化，与各种神经退行性疾病密切相关。特别是铁被认为会产生自由基，诱导氧化损伤，最终导致阿尔茨海默病（AD）。然而，传统的生物医学技术，如组织学染色，在研究这些无机沉积物的化学成分和价态方面存在局限性。我们应用常见的物理（phys-）科学方法，如 X 射线能量色散光谱（EDS）、聚焦离子束（FIB）和电子能量损失光谱（EELS），结合磁共振成像（MRI）、组织学和光学显微镜（OM），研究 AD 患者大脑中铁沉积物的价态。亚铁离子存在于来自三名 AD 患者的脑组织中的所有沉积物中，占每个标本中铁总量的 0.22-0.50。这些物理技术在医学科学中很少使用，具有为生物医学问题提供独特见解的巨大潜力。
