Blood Based Biomarker for Optimization of Early and Differential Diagnosis of Alzheimer's Dementia

Abstract

Dementia in Alzheimer´s disease is a global challenge. There is growing evidence that investigating blood biomarkers to diagnose Alzheimer´s disease is a promising fast, minimally invasive, and less costly method. The aim of this study was to review available studies on promising biomarkers for Alzheimer´s disease. The latest studies were collated for this review. Immunoassays followed by mass spectrometry and immunomagnetic reduction were reported to be highly relevant methods for detecting amyloid-ß 42 (Aß42) and amyloid-ß 40 (Aß40) to calculate the Aß42/Aß40 ratio, thereby improving the early diagnosis of Alzheimer´s disease. Amyloid-ß (Aß) peptides in blood plasma were considered as potential markers, as they correlated with the brain's Aß pathology. Phosphorylated tau protein 181 (p-tau181), phosphorylated tau protein 217 (p-tau217) and phosphorylated tau protein 231 (p-tau231) in blood samples assessed via Simoa technology served as parameters for the early and differential diagnosis of AD, and were markers of tau pathology in the brain. Neurofilament light chain (Nfl) and glial fibrillary acid protein (GFAP) were additional markers possibly facilitating the assessment of axonal and astroglial brain damage in Alzheimer´s disease. GFAP in blood was useful as an additional marker to detect early and to predict the time course of Alzheimer´s disease. Determining blood biomarkers represents less invasive and less costly diagnostics for Alzheimer´s disease. The investigation of blood biomarkers such as the Aß42/Aß40 ratio, p-tau217, p-tau231, Nfl and GFAP have been promising in establishing the AT(N) classification for Alzheimer´s disease. High-throughput methods should be evaluated in large patient cohort studies and via meta-analyses of studies. Consensus criteria with standard protocols for measuring these biomarkers while considering ethical issues and Alzheimer´s phenotype should unify normative values from different laboratories. The AT(N) classification of Alzheimer´s disease in blood would be a key element towards the implementation of minimally-invasive precision medicine.