New developments and future opportunities in biomarkers for amyotrophic lateral sclerosis

Abstract

Modern technology has improved the ability to probe effectively the underlying biology of ALS by examination of genomic, proteomic and physiological changes in patients with ALS, as well as to monitor functional and structural changes during the course of disease. While effective treatments for ALS are lacking, the discovery of sensitive biomarkers to disease activity offers clinicians tools for rapid diagnosis and insights into the pathophysiology of ALS. The ultimate aim is to lessen reliance on clinical measures and survival as trial endpoints and broaden the therapeutic options for patients with this disease.

Amyotrophic Lateral Sclerosis, Neuroimaging, Magnetic Resonance Imaging

“…These advanced techniques are surface and voxel based morphometry. The first is known as "cortical thickness measure" because it allows decomposition of cortical volume into both thickness and surface area and respects cortical topology [18]. The second, voxel base morphometry, allows the regional assessment of grey-matter (GM) and white matter density (WM) [5].…”

“…Post-mortem histopathological studies have demonstrated widespread cerebral white matter tract damage in ALS and this alteration can now be detected non-invasively using diffusion tensor imaging [18].…”

“…This neuroimaging method is based on a contrast imaging blood oxygenation level-dependent (BOLD) [18]. There are two main types of fMRI: task-associated fMRI, if associated with an external stimulus/task and resting-state fMRI, if the focus is on the evaluation of spontaneous fluctuations in BOLD [5].…”

“…MRI-S allows quantification of cerebral tissue metabolites non-invasively [18]. The evaluated parameters include, among others, N-acetylaspartate (NAA), a marker for neuronal function, total creatine (Cr), that reflects cellular energy reserves and total Choline (Cho), an indicator of cell membrane turnover [58]; Decreased NAA/Cho ratio is consistent with neuronal dysfunction [59] and NAA/Cr ratio may act as a biomarker of neuronal integrity [60].…”

“…The evaluated parameters include, among others, N-acetylaspartate (NAA), a marker for neuronal function, total creatine (Cr), that reflects cellular energy reserves and total Choline (Cho), an indicator of cell membrane turnover [58]; Decreased NAA/Cho ratio is consistent with neuronal dysfunction [59] and NAA/Cr ratio may act as a biomarker of neuronal integrity [60]. This indexes have been the most widely studied due to their simple spectral pattern and high concentrations in CNS [18].…”