Advanced Imaging and Molecular Biomarkers for the Early Diagnosis and Phenotyping of Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration. This review evaluates advanced imaging and molecular biomarkers for early diagnosis and phenotyping, including amyloid-PET (e.g., florbetapir), tau-PET (e.g., flortaucipir), CSF Aβ42/40 ratio, phosphorylated tau (p-tau181/217), and plasma neurofilament light (NfL). Innovations in hybrid PET/MRI and ultrasensitive immunoassays enable detection of AD pathology 10–15 years before clinical onset. We discuss biomarker-guided frameworks (NIA-AA, ATN) for staging AD continuum and differentiating subtypes (e.g., limbic-predominant vs. hippocampal-sparing). Challenges in standardization, accessibility, and cost are addressed, with future directions emphasizing AI-driven integration of multi-modal data and novel biomarkers (e.g., synaptic proteins, exosomal miRNAs) for precision medicine.