NEUROLOGICAL BIOMARKERS FOR EARLY DIAGNOSIS OF ALZHEIMER'S DISEASE: AN INTEGRATIVE LITERATURE REVIEW

Abstract

Objective: To analyze the available scientific evidence on neurological biomarkers used for early diagnosis of Alzheimer's disease (AD), evaluating their diagnostic accuracy and predictive capacity for disease progression. Methods: This is an integrative literature review conducted according to the guidelines proposed by Whittemore and Knafl (2005) and the PRISMA protocol. The search was performed in PubMed/MEDLINE, SciELO, BVS, and LILACS databases, covering publications from 2016 to 2026. Controlled descriptors indexed in DeCS/MeSH vocabularies were used, combined with Boolean operators. Studies were selected by two independent reviewers, with disagreements resolved by consensus. Methodological quality was assessed using QUADAS-2 for diagnostic accuracy studies, AMSTAR-2 for included systematic reviews, and the Newcastle-Ottawa Scale for observational studies. Results: A total of 2,450 records were identified in the consulted databases. After removing duplicates (n = 630) and title/abstract screening (n = 1,585), 235 studies were read in full, of which 18 met the eligibility criteria and were included in the synthesis. Cerebrospinal fluid (CSF) biomarkers — particularly Aβ42, total tau, and phosphorylated tau (p-tau) — showed high diagnostic accuracy (AUC 0.85–0.97). Blood-based biomarkers, such as plasma p-tau217 and the Aβ42/40 ratio, demonstrated diagnostic performance comparable to CSF with the advantage of minimally invasive access. Neurofilament light chain (NfL) correlated with neurodegenerative progression. Neuroimaging biomarkers — amyloid PET, tau PET, and structural MRI — confirmed pathological deposits decades before clinical onset. Conclusions: Neurological biomarkers represent reliable and promising tools for early AD diagnosis, especially in preclinical and prodromal phases. The combination of high-precision blood-based biomarkers with clinical criteria represents a viable strategy for population screening. Longitudinal and clinical validation studies are needed to consolidate cost-effective and accessible diagnostic protocols.