CEREBROSPINAL FLUID SEDIMENTS AS A RESERVOIR OF POTENTIAL BIOMARKERS

Cerebrospinal fluid (CSF) samples are extensively used to identify biomarkers for neurodegenerative diseases, but they are routinely centrifuged, and the resulting sediment or pellet is removed to eliminate cellular debris and other high-density particles. This standard practice raises a critical question: could these discarded sediments harbour potential biomarkers relevant for the diagnosis and prognosis of certain brain diseases? The aim of the present study is to investigate whether CSF sediments contain brain-derived components relevant to specific brain diseases and, thus, to substantiate the potential presence of biomarkers within these sediments.
To this end, we analysed CSF pellets from one Alzheimer’s disease case and one progressive supranuclear palsy case, by using transmission and scanning electron microscopy techniques (TEM and SEM, respectively), along with compositional analysis through SEM combined with energy-dispersive X-ray spectroscopy (SEM-EDX), as well as immunofluorescence and histochemical analyses on semithin pellet sections.
CSF pellets were found to contain brain-derived structures, including wasteosomes and psammoma bodies. Disease-relevant proteins were also detected in the CSF sediments: the sediment from the Alzheimer’s disease case contained both tau and Aβ42, whereas that from the progressive supranuclear palsy case contained tau, thus reflecting the specific proteinopathy.
These findings challenge the conventional practice of discarding CSF pellets, suggesting that clinically relevant substances may be systematically overlooked, and open new avenues for the discovery of biomarkers in neurodegenerative diseases.