Viscoelastic and Morphologic Changes in the Lumbar Intervertebral Discs of the 5xFAD Mouse Model of Alzheimer's Disease.

Abstract

Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD. The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD. Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we measured the lumbar IVD's extracellular matrix composition, the three-dimensional structure, histopathological degeneration, and mechanical behaviour. The amount of collagen, glycosaminoglycans, and advanced glycation end-products in the IVD did not differ in the 5xFAD animals. Likewise, the 5xFAD IVDs were not histopathologically degenerated. However, the IVD volume, measured by contrast-enhanced microCT, was larger in the 5xFAD animals (<i>p</i> = 0.046; 1-β = 0.53; Cohen's d = 1.19). Morphologically, the 5xFAD IVD heights were homogeneous and flatter than the WT IVDs (<i>p</i> = 0.043; 1-β = 0.60; Cohen's d = 1.41). Finally, dynamic micro compression revealed that 5xFAD IVDs have higher loss tangent (<i>p</i> = 0.0062; 1-β = 0.85; Cohen's d = 1.60) and greater energy dissipation (<i>p</i> = 0.0379; 1-β = 0.55; Cohen's d = 1.21). Shifts in viscoelastic behaviour and disc morphology are associated with early tissue degradation and affect the IVD's ability to efficiently recover from mechanical loading, predisposing the IVD to eventual degeneration. This work suggests that IVD's structure, morphology, and mechanics are affected by AD. Future work will focus on defining the molecular mechanisms of these changes in the IVD and their consequences in individuals with AD.