Single brain scans miss Alzheimer's complexity; doctors need combined tests
A major review reveals that PET imaging alone cannot capture the full picture of Alzheimer's disease progression, forcing clinicians to combine brain scans with blood and spinal fluid tests for accurate staging. This integrated approach matters to pharma companies developing treatments and healthcare systems planning diagnostic infrastructure, as it signals a shift toward more complex—and costly—multi-test protocols.
Originaltitel: Integration over reduction: multimodal PET and fluid biomarkers in Alzheimer's disease and beyond
PURPOSE OF REVIEW: Biomarker-based Alzheimer's disease (AD) diagnosis has shifted clinical practice from syndromic, dementia-stage diagnosis to a biologically defined framework anchored in amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) assays. However, binary amyloid/tau status does not capture disease complexity, stage, and the impact of co-existing neuropathologies. Here, we review in vivo human PET-fluid biomarker studies in AD and related neurological disorders. RECENT FINDINGS: We highlight how PET readouts of aggregated pathology and fluid biomarkers reflect related yet non-identical processes, and what relevant insights for staging and prognosis can be derived from it. We review recent efforts to infer tau stage from plasma and CSF markers, emphasizing stage-dependent relationships between soluble p-tau, amyloid burden, and tau-PET signal, and associated limitations that are partly driven by the lack of standardized tau PET staging methods. Finally, we examine how co-pathologies and biological modifiers - including age, APOE ε4, sex, and neuroinflammatory states - shape PET-fluid coupling and contribute to disease course. The reviewed evidence supports a complementary, multimodal biomarker approach that integrates PET with CSF and plasma measures. SUMMARY: To maximize insights from multimodal signals, harmonized integration frameworks - supported by neuropathology-anchored and real-world validation and explicitly accounting for modifiers such as age, sex, and APOE ε4 - will be essential.