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Integration over reduction: multimodal PET and fluid biomarkers in Alzheimer's disease and beyond
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DOI：10.1097/WCO.0000000000001462.png)
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Abstract
En 中文
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 epsilon 4, 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 epsilon 4 - will be essential.
Keywords:
Alzheimer's disease
disease staging
positron emission tomography-fluid biomarker coupling
precision medicine
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4.4
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2.8K
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