Circulating Biomarkers for the Early Diagnosis of Alzheimer's Disease

Abstract

With a rapidly growing incidence and prevalence, Alzheimer's disease (AD) is rapidly becoming one of the most disabling, lethal, and expensive diseases of the century. To diagnose AD as early as possible, the scientific world struggles to find reliable and non-invasive biomarkers that could predict the conversion of mild cognitive impairment to AD and delineate the ongoing pathogenic vicious pathways to be targeted with therapy. Research supports the use of blood biomarkers, such as Aβ_1-42/Aβ_1-40 ratio, phosphorylated tau181, and p-tau217 for diagnostic purposes, although the cut-offs are not clearly established and can depend on the assays used. For more accurate diagnosis, markers of neurodegeneration (neurofilament light) and neuroinflammation (glial fibrillary acidic protein) could be introduced in the biomarker panel. The recent approval of the Lumipulse G p-tau217/Aβ_1-42 plasma ratio by the FDA for the early detection of amyloid plaques associated with Alzheimer's disease in adult patients, aged 55 years and older, exhibiting signs and symptoms of the disease represents a significant advancement in the diagnosis of Alzheimer's disease, offering a more accessible and less invasive way to diagnose this devastating disease and allow potentially earlier access to treatment options.

Keywords: Alzheimer’s disease; amyloid beta; blood-based biomarkers; exosomes; glial fibrillary acidic protein; miRNAs; neurofilament light; phosphorylated tau.

Figure 1

Summary of the analytical platforms with best performances in detecting and measuring blood-based biomarkers in the diagnosis of Alzheimer’s disease. BBB—blood–brain barrier; LC-MS—liquid chromatography-mass spectrometry; ECL—electrochemiluminescence; Simoa—single-molecule array; p-tau—plasma phosphorylated tau; Aβ—amyloid beta; GFAP—glial fibrillary acidic protein; NfL—neurofilament light.