Diagnostic Complementarity of Cerebrospinal Fluid Biomarkers and Positron Emission Tomography in Early Alzheimer’s Disease

Alzheimer's Disease, classified as the most common form of dementia, remains one of the most difficult neurodegenerative conditions to detect early, as its defining molecular hallmarks, beta amyloid accumulation and tau hyperphosphorylation, emerge decades before clinical symptoms. As biomarker-driven diagnostics grow central to modern neurology, cerebrospinal fluid assays and positron emission tomography imaging have become two of the most influential tools in characterizing preclinical pathology. Yet their individual diagnostic performances and combined diagnostic implications in strengthening detection of preclinical and prodromal Alzheimer’s disease have not been fully unified across contemporary research. To address this gap, a targeted literature analysis of studies published from January 2011 to August 2025 was conducted across PubMed, Google Scholar, Embase, and Scilit using advanced biochemical and imaging keyword architectures. The synthesized findings demonstrate that cerebrospinal fluid biomarkers capture consistent early biochemical shifts, including substantial declines in Aβ42 associated with plaque deposition alongside transient elevations during early aggregation, as well as marked increases in phosphorylated tau reflecting neurofibrillary change. Positron emission tomography complements these data by quantifying the spatial distribution and regional burden of amyloid and tau aggregates, with PET-derived patterns aligning closely with cognitive trajectories and disease staging. Together, these biomarkers form a convergent diagnostic profile in which cerebrospinal fluid abnormalities often precede PET-detectable pathology, reinforcing a multimodal model of Alzheimer’s progression. These findings support integrating multimodal biomarkers, standardizing across laboratories, and expanding low-burden clinical platforms to enable accessible, precision-oriented diagnostic strategies that identify Alzheimer’s disease during preclinical and prodromal stages, before substantial neurodegeneration occurs.