Cerebrospinal fluid/plasma albumin quotient in dementia: a systematic review of biomarker potential and clinical associations.
Cerebrospinal fluid/plasma albumin quotient in dementia: a systematic review of biomarker potential and clinical associations.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Copenhagen, DK · Author affiliation
Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK 2100, Copenhagen, Denmark. Christian.sandoee.musaeus@regionh.dk.Location evidence
Glostrup, DK · Author affiliation
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.Location evidence
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Original abstract
The blood-cerebrospinal fluid barrier (BCB) maintains central nervous system homeostasis. Its dysfunction, reflected by an increased cerebrospinal fluid/plasma albumin ratio (Q-Alb), has been reported in several neurodegenerative diseases. However, the diagnostic utility of Q-Alb in dementia remains uncertain. This review aimed to systematically evaluate Q-Alb as a biomarker in dementia by examining inter-group differences, diagnostic performance, and associations with other biomarkers. To address this questions, PubMed was searched for observational and longitudinal studies reporting Q-Alb in patients with dementia and healthy controls (HC). Data on Q-Alb levels, diagnostic accuracy, and biomarker associations were extracted. Meta-analyses were performed for Alzheimer's disease (AD) and vascular dementia (VaD). The search identified forty-three studies, spanning AD, VaD, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Q-Alb was significantly higher in VaD compared with HC (pooled standardized mean difference 0.69, 95% CI: 0.53-0.86) and moderately increased in AD compared with HC (0.25, 95% CI: 0.14-0.36). Only two studies directly investigated the diagnostic accuracy. Q-Alb correlated positively with IgG index, neurofilament light chain, and vascular and inflammatory markers. Taken together, these findings suggest that Q-Alb is not a reliable standalone diagnostic biomarker, particularly for AD, but is consistently elevated in VaD and disorders with subcortical or vascular pathology. Findings support its role as a supportive marker of blood-cerebrospinal fluid barrier dysfunction. Further large, multimodal studies integrating vascular imaging are warranted to clarify its diagnostic and prognostic utility.