Examination of Alzheimer's disease by a combination of electrostatic force and mechanical measurement

Abstract

Alzheimer's disease (AD) is the most common dementia and neurodegenerative disorder disease in central nervous system, and threatens the people's health seriously. But till now there are no effective ways to diagnose and treat AD. Herein, the differences between charge propagation, surface morphology, and Young's modulus of the hippocampus, in healthy and AD mice have been investigated using advanced modes of Atomic Force Microscopy (AFM). The ability of charge transfer in AD samples has decreased compared with healthy samples. There are compact layered structures in hippocampus from healthy sample, whereas there are no obvious layered structures in hippocampus from AD sample. The Young's modulus of hippocampus from AD sample is about half of that from healthy sample. The results demonstrate that AFM will be helpful in the further study of the functions of hippocampus and pathogeny of AD. LAY DESCRIPTION: Alzheimer's disease is the most common cause of dementia, a neurodegenerative disease which especially affects elderly people, threatens people's health seriously. The pathological features of AD are senile plaques, neurofibrillary tangles, and cerebral atrophy. The main clinical symptoms of AD are progressive memory impairment, cognitive dysfunction, and loss of language skills, as there are disorder in limbic and cortices. The morbidity rate increases with age and is currently at 5% and 20% among people older than 65 and 85, respectively. Thus AD has a heavy socioeconomic burden, especially in an aging society. So far, there are no effective therapeutic clinical treatments, and no effective means and methods to test and diagnose early stage AD. This means that further studies are essential to gain a deeper, fundamental understanding of the pathogenesis of AD. In this work, the surface morphology, electrical and mechanical properties of the hippocampi from healthy and AD mice have been investigated by Atomic Force Microscopy (AFM) at nanometre scale for the first time. The hippocampi from healthy mice are composed of compact layered structures, whereas there are no obvious characteristic features in the hippocampi from AD mice. The electrical properties of hippocampus slices were studied by the Electrostatic Force Microscopy (EFM) mode of AFM. The charge propagation ability of axons from AD mice has decreased dramatically compared to that of healthy mice. After charge injection (injection voltage was +10 V) the charge density was 2.3 × 10⁵ C μm^-2 in healthy samples, which was larger than that from the AD samples (1.0 × 10⁵ C μm^-2 ). The Young's modulus of hippocampi from healthy and AD mice were 104.0 and 40.1 kPa, respectively, as revealed by the quantitative nanomechanical mapping (QNM) mode of AFM. It indicates that when AD occurs, the Young's modulus will be lower than the healthy sample. These observations and experimental approaches will be useful in future studies of the pathogeny of AD.

Keywords: Alzheimer's disease; atomic force microscopy; electrostatic force microscopy; hippocampus; young's modulus.