Plasma biomarkers in neuropsychiatric syndromes: A narrative review
PMCID: PMC12722585
PMID: 41284585
Abstract
Neuropsychiatric symptoms (NPS) are common features of neurodegenerative disease (NDD) but are relatively understudied compared to cognition, especially regarding biomarkers. Further, emerging evidence describes the utility of systematic assessment of NPS across the cognitive continuum, even in advance of dementia. In this narrative review, we discuss the role of plasma biomarkers in relation to NPS across the cognitive continuum of unimpaired, subjective cognitive decline, mild cognitive impairment, and dementia. While Alzheimer's disease is the primary focus, vascular, Lewy body, and frontotemporal dementia etiologies are also discussed. Literature searches included NPS and dementia-related search terms with additional literature identified based on the author group's subject area expertise. We found that plasma biomarkers are a burgeoning field, and scalability and accessibility make them well-suited for the study of NPS across the disease continuum. In early-stage NDD, diagnostic biomarkers are best suited for discriminating NDD-related NPS from non-NDD psychiatric syndromes and/or NPS due to other causes. In those with dementia, monitoring and prognostic biomarkers may enable the assessment of treatment response or help predict the risk of worsening symptoms. We conclude that plasma amyloid-β and tau show great promise in assessing NPS, especially during early-stage disease, but inflammatory and genetic biomarkers may also play a role across the disease course. Systematic research is required, keeping in mind the ethical considerations of knowing biomarker status in early-stage disease.
Full Text
Several sources of variation and pre-analytical factors should be considered when interpreting AD blood-based biomarkers. These factors range from circadian rhythms, dietary influences, and other person-specific variables to the collection and processing of the blood samples.
Pre-analytical factors that may affect levels of blood Aβ, p-tau, total tau, NfL, or GFAP include the collection tube type (e.g., anticoagulant used), time to centrifugation and storage, and storage temperature (Table 1).
Other sources of variability include protein instability following multiple freeze-thaw cycles and the distinct sensitivities of antibodies used in different assays. Aβ42 is sensitive to pre-analytical factors, but even more so is total tau, for which details such as time to centrifugation and centrifugation temperature are essential variables.
Certain factors may mitigate some of this variability, including fully automated technologies, ultrasensitive approaches, multiplexing, and rigorous standards such as those required in Clinical Laboratory Improvement Amendments (CLIA)-certified labs. Wider adoption of standardized pre-analytic protocols across global centers is recommended to ensure consistency, improve the reproducibility of tests, and minimize variability of results.
Longitudinal studies that find associations between NPS and plasma biomarkers throughout the AD continuum while considering the presence of MBI are in high demand. These studies could suggest mechanistic relationships to elucidate how NPS and neuropathology evolve over time, and address if proper therapy may modify such relationships. Systematic reviews that identify, select, synthesize, and appraise all high-quality research evidence relevant to the associations of NPS with plasma biomarkers will be needed when more original studies are available. Actionable items have been drafted to achieve these goals (Table 2).
Sections
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Metadata
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