Advanced biomarkers: Beyond amyloid and tau: Emerging non-traditional biomarkers for alzheimer`s diagnosis and progression

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder that leads to progressive cognitive decline and imposes a significant socio-economic burden. Traditional diagnostic methods, primarily based on amyloid-beta (Aβ) and tau biomarkers, often identify the disease at late stages, highlighting the need for more sensitive and accessible early detection tools. This review explores emerging non-traditional biomarkers, including salivary, lipid, urinary, synaptic, blood-based, microRNA (miRNA), cerebrospinal fluid (CSF), fecal, and inflammatory markers, which provide deeper insights into AD pathophysiology. These biomarkers reflect key pathological processes such as neuroinflammation, mitochondrial dysfunction, oxidative stress, synaptic damage, lipid dysregulation, and genetic factors. Non-invasive biomarkers, such as those found in saliva and urine, present promising avenues for large-scale screening, while advanced blood-based markers like neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) offer precise monitoring of neurodegeneration and inflammation. Additionally, miRNAs and lipid biomarkers shed light on molecular alterations in neuronal health and signaling. Integrating these biomarkers with imaging techniques, proteomics, and genetic profiling enhances diagnostic accuracy and enables personalized treatment approaches. This shift toward multi-dimensional biomarker assessment not only improves early detection but also aids in tailoring therapeutic strategies to individual disease profiles. By reviewing recent advancements, this article highlights the transformative potential of emerging biomarkers in overcoming the limitations of conventional diagnostics. Standardization and validation across diverse populations will be crucial in expanding their clinical applicability, ultimately improving disease management, reducing societal burden, and enhancing the quality of life for individuals affected by AD.