Neurochemical Biomarkers in Alzheimer’s Disease: A Practical Narrative Review of Analytical and Clinical Interpretation

Abstract

Over the past years, there has been an evident change in the perspective of the Alzheimer disease field where descriptive clinical diagnosis has been replaced by a biological one where molecular marker that indicate amyloid deposition, tau protein phosphorylation abnormalities, and the degree of neuron and glial damage are measured. Aβ42, Aβ40, and the Aβ42/Aβ40 ratio, as well as total tau, p-tau181, p-tau217, p-tau231, neurofilament light chain (NfL) and GFAP, the most established neurobiological markers in this area, as they connect the disease on the one hand, and the possibility of early detection, biomarker classification, and longitudinal follow-up on the other. The purpose of the review is to put these markers in a practical context based on the nature of the biological sample and the laboratory platforms to measure them, the distinctions between conventional and automated immunoassays, ultra-sensitive Simoa methods, and LC-MS/MS mass spectrometry, and to discuss the strengths and weaknesses of each method. The review also covers issues of pre-analysis, analytical validation, compatibility with the platform and derivation of cutoff values, and then considers future trends that lead to more clinically useful blood tests, such as automated tests and those that have recently undergone sophisticated regulatory review. The review finds that the real worth of these biomarkers is not just in their availability but also in choosing the right biomarker to the right clinical question and in maintaining the integrity of the measurement chain between sample collection and interpreting the results.