Blood Biomarkers for Amyotrophic Lateral Sclerosis: Myth or Reality?

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal condition primarily characterized by the selective loss of upper and lower motor neurons. At present, the diagnosis and monitoring of ALS is based on clinical examination, electrophysiological findings, medical history, and exclusion of confounding disorders. There is therefore an undeniable need for molecular biomarkers that could give reliable information on the onset and progression of ALS in clinical practice and therapeutic trials. From a practical point of view, blood offers a series of advantages, including easy handling and multiple testing at a low cost, that make it an ideal source of biomarkers. In this review, we revisited the findings of many studies that investigated the presence of systemic changes at the molecular and cellular level in patients with ALS. The results of these studies reflect the diversity in the pathological mechanisms contributing to disease (e.g., excitotoxicity, oxidative stress, neuroinflammation, metabolic dysfunction, and neurodegeneration, among others) and provide relatively successful evidence of the usefulness of a wide-ranging panel of molecules as potential biomarkers. More studies, hopefully internationally coordinated, would be needed, however, to translate the application of these biomarkers into benefit for patients.

Role of diffusion tensor imaging or magnetic resonance spectroscopy in the diagnosis and disability assessment of amyotrophic lateral sclerosis

“…For the UMNs, neuroimaging techniques are a promising way to diagnose ALS or evaluate disease progression, and these techniques include conventional MRI, DTI, MRS and functional MRI [8]. Limb onset and older age can delay an ALS diagnosis [9].…”

Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP‐43 subcellular distribution

“…Genetic and non‐genetic forms are clinically indistinguishable . ALS, besides being a multifunction and multifactorial disease, is a multisystem disease affecting not only motor neurons, but also other cells and tissues, such as glia as well as cells of the immune system and skeletal muscle .…”

Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

“…There is a need for a biomarker of disease progression in amyotrophic lateral sclerosis (ALS), to assist with prognosis and for use in clinical trials [1,2] with a blood biomarker being most convenient [3]. Neurofilament (Nf) heavy protein (NfH) is one of the three neuronal cytoskeleton intermediate filament subunit proteins; the others being neurofilament medium protein and light protein [4].…”