Viscoelastic Properties of Human Autopsy Brain Tissues as Biomarkers for Alzheimer's Diseases

Abstract

Objective: The present study investigates viscoelastic properties of human autopsy brain tissue via nanoindentation to find feasible biomarkers for Alzheimer's disease (AD) in ex vivo condition and to understand the mechanics of the human brain better, especially on the difference before and after progression of AD.

Methods: Viscoelastic properties of paraformaldehyde-fixed, paraffin-embedded thin (8 [Formula: see text]) sectioned normal and AD affected human autopsy brain tissue samples are investigated via nanoindentation with a combined loading profile of a linear preloading and a sinusoidal loading at various loading frequencies from 0.01 to 10 [Formula: see text]. In 1200 indentation tests for ten human autopsy brain tissue samples from ten different subjects (five AD cases and five normal controls), viscoelastic properties such as Young's modulus, storage modulus, loss modulus, and loss factor of both gray and white matter brain tissues samples from normal and AD affected tissues were measured experimentally.

Results: We found that the normal brain tissues have higher Young's modulus values than the AD affected brain tissues by 23.5 % and 27.9 % on average for gray and white matter, respectively, with statistically significant differences ( ) between the normal and AD affected brain tissues. Additionally, the AD affected brain tissues have much higher loss factor than the normal brain tissues on lower loading frequencies.

Significance: AD is one of the leading causes of death in America and continues to affect a growing population. The challenges of recognizing the early pathological changes in brain tissue due to AD and diagnosing a patient has led to much research focused on finding biomarkers for the disease. In this regard, understanding the mechanics of brain tissues is increasingly recognized to play an important role in diagnosing brain diseases.

Fig. 1.

(a) Loading profile that consists of pre-loading, sinusoidal loading, and unloading phase, (b) resultant stress-strain curve obtained from the load and indentation depth measurement, and (c) stress-strain curve for the sinusoidal loading phase.

Fig. 2.

Experimental setup for viscoelastic characterization of the human autopsy brain tissue via nanoindentation: (a) brain tissue sample for the experiment, (b) nanoindentation system, and (c) schematic of the contact between the circular flat-ended tip and the sample.

Fig. 3.

Scanning electron microscope (SEM) images of normal and AD affected brain tissue.

Fig. 4.

Atomic force microscope (AFM) images of normal and AD affected brain tissue with surface roughness, R_a.

Fig. 5.

Stress-strain curves of human autopsy brain tissues obtained by the nanoindentation experiment: (a) gray matter of normal brain tissue, (b) white matter of normal brain tissue, (c) gray matter of AD affected brain tissue, and (d) white matter of AD affected brain tissue.

Fig. 6.

Measured Young’s modulus, E, of normal and AD affected human autopsy brain tissues during the pre-loading phase.

Fig. 7.

Experimental results of viscoelastic characterization for normal and AD affected human autopsy brain tissues: (a) storage modulus, E′, (b) loss modulus, E″, and (c) loss factor, η.