Blood-based biomarkers for Alzheimer’s disease: From bench to bedside

Abstract:

Alzheimer’s disease (AD) develops through a progressive neurodegenerative process. During this time, the body accumulates features of the disorder before cognitive impairment beginning. Therefore, an early diagnosis can be made, which is challenging with traditional methods. Traditional methods for diagnosing AD, include cerebrospinal fluid (CSF) biomarkers and positron emission tomography imaging, provide reliable detection of amyloid and tau pathology, their broad application is constrained by invasiveness, expensive, and restricted availability. Recently, the advances in blood-based biomarkers linked to Alzheimer’s pathology have provided an opportunity to diagnose AD with less expense and more rapidly. Advances in ultra-sensitive assays to detect plasma amyloid beta (Aβ) 42/Aβ40 ratios, phosphorylated tau isoform patterns, neurofilament light chains, and glial fibrillary acid proteins have demonstrated high specificity for AD. Using multiple biomarkers together in accordance with the ATN framework has shown greater diagnostic and prognostic abilities than any single marker. In addition, machine learning algorithms that incorporate blood biomarkers, genetic factors (APOE ε4), and clinical risk factors are providing more accurate and individualized risk assessments for AD than traditional statistical methods. This article summarizes the scientific basis of using multiple blood biomarkers for diagnosing AD, the clinical utility of these biomarkers based on their analytical performance, an overview of CSF and imaging biomarkers, an overview of blood biomarkers, and future directions for these blood biomarkers in diagnosing AD, classifying patients in clinical trials, and use in developing countries.