Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.

• Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

Humans

Biomarkers

cerebrospinal fluid

Alzheimer Disease

cerebrospinal fluid

diagnosis

Cerebrospinal Fluid Proteins

analysis

metabolism

Male

Female

Sensitivity and Specificity

Aged

Brain Diseases

cerebrospinal fluid

diagnosis

Middle Aged

Amyloid beta-Peptides

cerebrospinal fluid

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)