From Amyloid PET to Plasma Biomarkers: A Multimodal Imaging Framework for Early Diagnosis and Staging of Alzheimer's Disease.

INTRODUCTION:Alzheimer's disease (AD) is biologically defined by amyloid beta and tau pathology. Available biomarkers enable early diagnosis but differ in targets, accessibility, and utility. This review synthesizes evidence for plasma biomarkers, magnetic resonance imaging (MRI), and positron emission tomography (PET) to develop a pragmatic, stage-aware framework for early diagnosis and staging. METHODS:We conducted a narrative review of recent literature and professional guidance (2024-2026) covering plasma biomarkers; structural/functional MRI; and amyloid, tau, and fluorodeoxyglucose (FDG) PET. Evidence was organized by biological target, diagnostic role, disease stage, and intended-use population. RESULTS:For symptomatic individuals, high-performance plasma biomarkers (especially phosphorylated tau at threonine 217 [p-tau217]) support scalable triage and biological enrichment. MRI provides anatomical, differential-diagnostic, and treatment-safety information. Amyloid PET offers biological confirmation; tau PET adds regional staging and prognosis; FDG PET characterizes synaptic dysfunction and distinguishes dementia patterns. Emerging endogenously cleaved microtubule-binding region tau containing residue 243 (eMTBR-tau243) and brain-derived p-tau217 remain investigational. In cognitively unimpaired at-risk individuals, routine screening is not implied; use is for research or trial enrichment. DISCUSSION:The preferred pathway is sequential: clinical evaluation and MRI establish context, validated plasma tests guide referral, and PET resolves uncertainty or refines staging when results may change management. This resource-aware integration improves diagnostic specificity and treatment decisions. Prospective implementation studies are needed to validate thresholds and equitable performance across diverse settings.