Evolving Role of Biomarkers in Early Diagnosis and Prognosis of Alzheimer’s Disease

Alzheimer's disease (AD) is the leading cause of dementia globally, typified by insidious cognitive impairment underlain by amyloid-β plaques, neurofibrillary tangles, and neurodegeneration. Accumulating evidence shows these pathophysiological changes start years to decades before symptom onset, highlighting an urgent need for preclinical detection and prognostication. Biomarkers have revolutionized the field with the ability to measure amyloid deposition, tau pathology, and neuronal damage in vivo. The AT(N) framework has reconceptualized AD as a biologically based continuum, merging biomarkers across modalities. Cerebrospinal fluid and imaging assessments, including amyloid/tau PET and MRI-based volumetry, are still gold standards but are constrained by invasiveness and expense. New developments in blood-based biomarkers, particularly plasma phosphorylated tau (p-tau217, p-tau231), Aβ42/Aβ40 ratio, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), have proved to be highly accurate in identifying preclinical disease and forecasting cognitive decline. Head-to-head comparisons show that plasma p-tau217 is equally effective as tau PET in forecasting progression in cognitively unimpaired individuals, and repeated testing enhances prognostic precision. Multimodal biomarker integration provides greater predictive power, but standardization, diversity of populations, and preclinical diagnosis ethical issues persist. Potential future advances involve validation in large and heterogeneous cohorts, longitudinal follow-up, and incorporation of new markers like synaptic and inflammatory proteins. In summary, biomarkers are revolutionizing early diagnosis and prognosis of AD, making possible earlier intervention and therapeutic customization.