Molecular Biomarkers of Neurodegenerative Disorders: A Practical Guide to Their Appropriate Use and Interpretation in Clinical Practice

Abstract

Neurodegenerative disorders (NDs) represent a group of different diseases characterized by the progressive degeneration and death of the nervous system's cells. The diagnosis is challenging, especially in the early stages, due to no specific clinical signs and symptoms. In this context, laboratory medicine could support clinicians in detecting and differentiating NDs. Indeed, biomarkers could indicate the pathological mechanisms underpinning NDs. The ideal biofluid for detecting the biomarkers of NDs is cerebrospinal fluid (CSF), which has limitations, hampering its widespread use in clinical practice. However, intensive efforts are underway to introduce high-sensitivity analytical methods to detect ND biomarkers in alternative nonivasive biofluid, such as blood or saliva. This study presents an overview of the ND molecular biomarkers currently used in clinical practice. For some diseases, such as Alzheimer's disease or multiple sclerosis, biomarkers are well established and recommended by guidelines. However, for most NDs, intensive research is ongoing to identify reliable and specific biomarkers, and no consensus has yet been achieved.

Keywords: Alzheimer’s disease; Parkinson’s disease; biomarker; laboratory medicine; neurodegeneration.

Figure 1

Molecular biomarkers of neurodegenerative disorders. Aβ42, β-amyloid 42; Aβ40, β-amyloid 40; p-tau, tau phosphorylated at threonine 181; α-syn, α-synuclein; CgA, chromogranin A; λFLC, free light-chain lambda; κFLC, free light-chain kappa; mHTT, mutated huntingtin protein; NfL, neurofilament lights; pNfH, phosphorylated neurofilament heavy; OCB, oligoclonal bands; TDP-43, TAR DNA-binding 43.

Figure 2

Blood (A) and cerebrospinal fluid; (B) sample separation protocol. CSF, cerebrospinal fluid; α-syn, α-synuclein; NfL, neurofilament lights; NfH, neurofilament heavy; Ng, neurogranin; κFLC, free light-chain kappa; λFLC, free light-chain lambda; Aβ40, β-amyloid 40; Aβ42, β-amyloid 42; t-tau, total tau; p-tau, tau phosphorylated at threonine 181.