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 μm) 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 -10 Hz. In 1,200 indentation tests for 10 human autopsy brain tissue samples from 10 different subjects (5 AD cases and 5 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 (p < 0.0001) 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.

Standard‐space atlas of the viscoelastic properties of the human brain

“…These results also support some investigations conducted at the tissue level; a study that used microindentation on freshly resected, human brain tissue also reported that WM was stiffer than cortical GM when evaluated with various strain rates and relaxation function parameters (Finan, Sundaresh, Elkin, McKhann, & Morrison, 2017). Mechanical indentation tests have also revealed that GM is approximately one third softer than WM in the porcine (Kaster, Sack, & Samani, 2011; van Dommelen, van der Sande, Hrapko, & Peters, 2010) and bovine brain (Budday et al, 2015), although other studies from the microindentation literature have shown the opposite trend (Budday et al, 2017; Park, Lonsberry, Gearing, Levey, & Desai, 2019). The discrepancy is possibly due to investigations being performed at the microscale returning mechanical properties that differ from the macroscale properties measured with MRE.…”

Poro-Viscoelastic Effects During Biomechanical Testing of Human Brain Tissue

“…In recent years, it has increasingly been recognized that mechanical signals play an important role for brain development (Budday et al, 2015b;Koser et al, 2016;Thompson et al, 2019), injury (Meaney et al, 2014;Hemphill et al, 2015;Keating and Cullen, 2021), and disease (Murphy et al, 2016;Barnes et al, 2017;Gerischer et al, 2018;Park et al, 2018). In silico modeling based on the theory of nonlinear continuum mechanics has therefore proven a valuable tool to, on the one hand, computationally test hypotheses that complement experimental studies and provide a predictive understanding of processes in the brain under physiological and pathological conditions (Goriely et al, 2015;Budday et al, 2020).…”

Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer’s disease mouse model

“…The chronic neuroinflammation causes disease-related symptoms, such as loss of neurons and synapses ultimately leading to memory problems and dementia [13]. In addition to the underlying biological processes in AD, the investigation of mechanical properties received attention in recent years as a potential biomarker for early diagnosis, as shown by magnetic resonance elastography (MRE) studies where brain elasticity and viscosity decreased in AD human patients [14,15,16,17,18,19], and as a novel drug target for tissue regeneration [? 20].…”