BIOMARKERS IN ALZHEIMER'S DISEASE: A SYSTEMATIC REVIEW ON PATHWAYS TO EARLY DIAGNOSIS

Abstract

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative condition that initially manifests as mild cognitive impairment. Its symptoms reflect brain atrophy caused by the accumulation of beta-amyloid (Aβ) plaques and protein tangles, resulting in neuronal death. Objective: To analyze biomarkers for the diagnosis of Alzheimer's disease and describe collection methods. Material and Methods: The PUBMED and SCOPUS databases were consulted using the descriptors (“Alzheimer Disease”) AND (“biochemical markers”) AND (“neurodegenerative disease”) AND (“Biomarkers”). The inclusion criteria were articles published between 2019 and 2024, with a title and abstract relevant to the topic, which analyzed biochemical markers for the diagnosis of AD. Duplicates, reviews, book chapters and articles outside the scope were excluded. Results: After applying the inclusion criteria, 6 articles were selected from a total of 65. The most prevalent year was 2019 among the studies (n=3). 5 articles agree that the most relevant biomarkers are the decrease in Aβ42 and the increase in tau protein in the cerebrospinal fluid (CSF) and 1 article does not address these findings. Furthermore, 5 articles propose new biochemical markers.Discussion: Identifying AD biomarkers is essential for early diagnosis and management of the disease. The most used are Aβ and tau protein. Reduced Aβ42 and increased total tau (T-tau) and phosphorylated tau (P-tau) in CSF are considered the typical profile of AD. The decrease in Aβ42 reflects the accumulation of amyloid plaques in the brain, while the increase in T-tau and P-tau is related to neurodegeneration. However, analysis of these proteins requires CSF collection, an invasive procedure involving lumbar puncture. In contrast, non-invasive markers are under study, such as neurofilament light chain (NfL), which has plasma analysis. Elevated levels of NfL in plasma are indicative of neurodegeneration and are useful in screening for AD. Another novelty for biomarkers are peptide fragments of proteins such as fibrinogen and 2-HS glycoprotein. Similarly, genetic markers such as presenilin gene variants are associated with early-onset AD, while apolipoprotein E4 is an indicator of predisposition for late-onset AD. Conclusion: Therefore, even with advances, the clinical use of biomarkers still faces challenges. Aβ and tau are widely accepted, but invasive methods limit their application. New blood marker methods, such as NfL, help in the diagnosis of AD by offering less invasive alternatives.