Biomarkers for Early Detection of Alzheimer’s Disease: A Systematic Literature Review

Abstract

Alzheimer’s disease (AD) is a gradual neurodegenerative disorder that is associated with insidious cognitive impairment and a preclinical or pre-symptomatic phase whereby years may lapse between the onset of the neuropathological changes and clinical manifestation. Early and precise diagnosis is vital in intervention, stratification of patients and establishment of disease modifying therapies. This is a systematic literature review, which has compiled the existing evidence on known and emerging biomarkers of early detection of AD in preclinical and prodromal stages. In the overall search of the predefined inclusion criteria in PubMed, Google Scholar, and Science Direct, 1,095 records were found, and 174 papers were included in the qualitative synthesis. The result points to the valid diagnostic value of cerebrospinal fluid biomarkers, such as amyloid-24, total tau, phosphorylated tau, and high-level neuroimaging techniques, such as amyloid, tau positron emission tomography and structural magnetic resonance imaging. New blood-based biomarkers, especially plasma phosphorylated tau isoforms, neurofilament light chain, and glial fibrillary acidic protein, show significant prospective as minimally invasive scalable biomarkers. Multimodal combination of fluid, imaging and genetic markers is always associated with high diagnostics accuracy as opposed to single-modality. Although major improvements have been made, there are still major issues related to the standardization of assays, cost-effectiveness, its accessibility, and large-scale longitudinal validation. In general, the combination of fluid-based and imaging biomarkers is a radical change toward the biological basis of diagnosis and precision medicine in the context of Alzheimer disease.