Potential diagnostic markers in Alzheimer's disease: current perspectives and future directions

Alzheimer's disease (AD), the most common form of dementia, remains a leading neurodegenerative disorder that necessitates the development of diagnostic markers. While current cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers facilitate diagnostic accuracy, their invasive and pricey nature limits widespread application. Blood-based biomarkers, such as plasma Aβ42/40 and phosphorylated tau isoforms, are emerging as accessible alternatives. Biomarkers reflecting neurodegeneration (e.g. neurofilament light chain, brain-derived tau) and neuroinflammation (e.g. glial fibrillary acidic protein, TSPO-PET) provide additional insights into disease progression. Novel approaches - including exosomal and Aβ seeds biomarkers, omics techniques, and retinal imaging - further broaden the diagnostic landscape. Despite the promising perspectives, challenges remain in validity and utility. This review highlights recent advances of AD diagnostic markers, evaluates their clinical potential and limitations, and outlines future directions guided by the Geneva five-phase roadmap. The ultimate aim is to facilitate earlier detection and timely intervention of this burdensome disorder.